The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index; none of the 59 sources its claims cite is checked for support yet.
Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer
Open accessAbstract
Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.
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60 Own result · 33 Not checked yet · 20 Own interpretation · 14 Own method
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“For the 1L IO patients, 59% of Akk + patients were still alive after 12 months (OS ≥ 12) while only 35% of Akk -individuals were long term survivors (Figure 1E, p=0.04).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelationaln = 86- Asserted: passes — The authors put it forward as true.
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“As observed in our clinical cohort, resistance to therapy in mice was associated with the absence of detectable Akk in the FMT experiments (Extended Figure 2C-D).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > left panel).
plaincorrelationaln = 26- Asserted: passes — The authors put it forward as true.
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In the paper
“When considering the subgroup of patients who received immunotherapy alone as front-line treatment (1L IO, n=86), ORR were 41% and 19% in the Akk + versus Akk -respectively (Figure 1B, p=0.016).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelationaln = 86- Asserted: passes — The authors put it forward as true.
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“Using a Kernel density estimation of the relative abundance of Akk positionning patients with OS ≥ 12 or OS < 12, we noticed that patients harboring Akk high , at a relative abundance > 75 th percentile (4.656%), did cluster within the OS < 12 months (Figure 2B-C left panel, p=0.005).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, we found a significant increase in Shannon diversity in Akk low compared to Akk -or Akk high specimens (Extended Figure 4A, p=0.00003)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
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“The supervised analysis of significant gene expression differences between Akk + and Akk -groups within a panel of 395 immune-related genes of the Oncomine Immune Response Research Assay 39 revealed a set of differentally expressed genes associated with response to PD-1 blockade in lung cancer (Figure 1F)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
What the sources say
- Not checked yetcites [39] Hakozaki, T. et al. The gut microbiome associates with immune checkpoint inhibition outcomes in patients with advanced non-small cell lung cancer. Cancer Immunol. Res. 8, 1243–1250 (2020). source
plaincorrelationaln = 22- Asserted: passes — The authors put it forward as true.
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“LEfSe analysis within the Akk + group exhibiting OS ≥ 12 months versus those with OS < 12 months unveiled increased relative abundance of Lachnospiraceae family members (Dorea formicigenerans, D. longicatena, Eubacterium rectale, E. hallii, R. intestinalis, Coprococcus comes) in patients with OS ≥ 12.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, the relative abundance of Akk within the Akk + population ranged from 0.035% up to 66.210%.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“while feces from Akkpatients were overabundant in Veillonella parvula, Actinomyces and genus Clostridium (C.innocuum, Hungatella hathewayi) (Extended Figure 3B)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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“Not surprisingly, ECOG performance status ≥ 1 was another independent prognostic factor for this cohort 31 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
What the sources say
- Not checked yetcites [31] Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353.e21 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The Akk + group without ATB exposure showed the strongest clinical benefit (median OS of 23.0 months) compared to the three other groups (Extended Figure 5A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“with a significantly longer median OS for Akk low patients compared to Akk high (27.2months versus 7.8 months, Cox adjusted HR:0.38; 95%CI: 0.22-0.65,p=0.0005)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“as well as differences in the overall microbial community composition between both groups (Extended Figure 3A lower panel, p=0.0001).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The median OS of ≥ 2L NSCLC patients was 18.8 months for the Akk + group compared to 13.4 months in the Akk -group (HR=0.70;(95% CI :0.50-0.98);p=0.04, Figure 1D, Table S1A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Kaplan Meier survival curves using the trichotomic stratification according to Akk relative abundance diverged (logrank test p=0.0007, Figure 2D, Table S4A-B)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The multivariate Cox regression analysis indicated that Akk dictated NSCLC prognosis, more than PD-L1 did (p=0.012 in 235 patients, Figure 2E).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
hedgeddirectn = 235- Asserted: passes — The authors put it forward as true.
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In the paper
“and Akk -patients (27.2 months versus 15.5 months, adjusted HR:0.63; 95%CI:0.44-0.91,p=0.0150).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We found a significant increase of the Shannon diversity index (Extended Figure 3A upper panel, p<0.0001) in Akk + compared to Akk -patients”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“The presence of Akk in stools at diagnosis had no influence on histology (non-squamous vs squamous NSCLC (for multivariate analysis, p=0.556 in Table S1A, Table 1).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“We unexpectedly found an over-representation of Akk in patients with OS < 12 months within the Akk + group, suggesting that the relative abundance of Akk may influence prognosis more than its absolute presence or absence.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
hedgedcorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“When considering Akk + versus Akk -groups in our cohort, objective response rates (ORR) were 28% and 18% respectively (Figure 1A, p=0.04).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Variable importance plot (VIP) discriminant analysis of taxonomic stool composition revealed that the ecosystem abnormally enriched in Akk (Akk high ) was overrepresented by species of the genus Clostridium (Clostridium symbosium, C.innocuum, C. scindens, C. boltae, C. clostridioforme)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We confirmed that the overabundance of stool Akk at diagnosis in patients exposed to ATB was associated with lower overall survival despite ICI therapy (Extended Figure 5C, Figure 2G right panel).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Accordingly, ATB tended to reduce the alpha diversity of the Akk + group (Extended Figure 5B-C).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, exogenous Akkp2261 was not detectable more than 30 hrs in the recipient intestines (as shown in qRT-PCR using A. muciniphila specific probe sets).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Pre-clinical study details:
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“revealed that exogenous Akkp2261 was effective in about 50% cases”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Akk rescued response to PD-1 blockade by shifting the microbiome towards species associated with good prognosis
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Here, we provide preclinical data suggesting that Akk could therapeutically bypass the resistance to anti-PD-1 blockade conferred by FMT bereft of endogenous Akk (Extended Figure 6 and 17,18 ).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [17] Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018). source
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Surprisingly, in addition to acting as an independent negative prognostic factor, ATB promoted the overabundance of Akk (Akk high ) above the 77 th percentile level associated with poor prognosis.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, we failed to observe a similar trichotomic distribution correlating with opposite clinical outcome investigating other bacteria (Figure 3).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, we could restore responsiveness to PD-1 blockade, only in the setting of Akk -FMT (Extended Figure 6B-C).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Akk rescued response to PD-1 blockade by shifting the microbiome towards species associated with good prognosis
hedgeddirectn = 29- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, exposure to ATB showed the shortest OS (mOS around 9 months, Extended Figure 5A, p=0.017).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The oral supplementation with exogenous Akk (Akkp2261) was particularly effective when Akk shifted the recipient microbiome towards a healthy status (Extended Figure 6D-E).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, ATB exposure enriched the Akk + group in Gammaproteobacteria (E.coli), Clostridia class (Clostridium bolteae, Ruthenibacterium lactatiformens), and H2S producing bacteria (Bilophila wadsworthia) (Extended Figure 5D)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The non-supervised hierarchical clustering of the ratios between the tumor growth kinetics with anti-PD-1 mAbs with or without exogenous Akkp2261 normalized on the effect of PD-1 blockade in eubiotic conditions revealed that exogenous Akkp2261 was effective in about 50% cases (heatmap in the Extended Figure S3E).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Pre-clinical study details:
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“F. Principal Component Analysis (PCoA) of the differentially expressed genes according to intestinal prevalence of Akk, using the 395 immune-related gene selection of the Oncomine Immune Response Research Assay indicating significant differences using a Mann-Whitney p-value < 0.10 through PERMANOVA test using Euclidian distance.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The next favorable prognostic group fell into Akk -without ATB exposure, with a median OS of 16.0 months.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Shannon diversity index representing stool alpha diversity in Akk+ and Akk-groups of fecal specimens (N=338) (A, upper panel).”
- Also stated in: § Extended · plain
“Exact p-value: 3.84573e-05.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Extended · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, ATB use doubled the proportion of individuals presenting a stool Akk high phenotype.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“This phenotypic trait of overabundance of Akk > 4.799 was associated with a dominance of the Clostridium species (C.bolteae, C. innocuum, C. asparagiforme, C. scindens, C. symbosium) belonging to clusters IV and XIVa of the genus Clostridium, known to maintain IL-10 producing Treg in colonic lamina propria 47 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [47] van der Lugt, B. et al. Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1−/Δ7 mice. Immun. Ageing 16, 6 (2019). source
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In the paper
“There was an added value to consider the coordinated presence of both, Akk as well as E. hallii or B. adolescentis, to accurately predict ORR and/or mOS in this cohort of 338 NSCLC patients (Figure 3C,E).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on other components of the Akk -associated ecosystem
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition to depleting favorable genera associated with survival (such as Ruminococcus) 41 , ATB use tends to deviate the gut microbiome composition towards harmful bacteria previously associated with proinflammatory or immunoregulatory pathways (such as E. coli, and Clostridium bolteae) 46 , supporting previous findings in renal cell carcinomas amenable to ICI 37 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [41] Benevides, L. et al. New insights into the diversity of the genus Faecalibacterium. Front. Microbiol. 8, 1790 (2017). source
- Not checked yetcites [46] Ruusunen, A., Rocks, T., Jacka, F. & Loughman, A. The gut microbiome in anorexia nervosa: relevance for nutritional rehabilitation. Psychopharmacol. 236, 1545–1558 (2019). source
- Not checked yetcites [37] Hwang, S. et al. Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell lung cancer. Sci. Rep. 10, 643 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, even in avatar gut humanized mouse models, responders to exogenous Akkp2261 shifted their microbiome towards an over-representation of some of the above mentionned species belonging to the Akk + ecosystem.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
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In the paper
“We found a drastic increase of the proportion of Akk high patients among ATB users versus non users (40% versus 19%, p=0.023, Figure 2F).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
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In the paper
“Interaction between ATB and A.muciniphila on survival and microbiome composition.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“species significantly associated with or excluded from Akk -enriched ecosystems (Akk + , blue dots, Akk -, red dots)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“Stool A. muciniphila (Akk) is associated with ICI clinical benefit.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“We found msp_0025 to correspond to SGB9226, and used its relative abundance values as a proxy for A. muciniphila in MetaOMineR.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Human stool samples and metagenomics analyses
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In the paper
“We detected taxonomic differences in the recipient microbiota in responders (R) versus non responders (NR) to exogenous Akkp2261 (Extended Figure6Eright panel).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
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In the paper
“Supporting this contention, we and others reported that primary responses to anti-PD-1/ PD-L1 antibodies in patients with epithelial tumours and melanoma could, at least in part, be attributed to the taxonomic composition of the gut microbial ecosystem 18,20,25 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [20] Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018). source
- Not checked yetcites [25] Santoro, A. et al. Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell. Mol. Life Sci. 75, 129–148 (2018). source
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In the paper
“However, only a minority (35%) of patients benefit from sustained response to ICI 8 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [8] Ferrara, R. et al. Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol. 4, 1543–1552 (2018). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, antibiotics (ATB) prior to ICI initiation drastically reduced the clinical benefit in several cohorts of patients across various cancer types (melanoma, advanced NSCLC, renal cell carcinoma (RCC), and urothelial cancer) 18,[20][21][22] .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [20] Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018). source
- Not checked yetcites [21] Derosa, L. & Zitvogel, L. Antibiotics impair immunotherapy for urothelial cancer. Nat. Rev. Urol. 17, 605–606 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“First, in pre-clinical models, experiments with germ-free or antibiotic (ATB)treated mice unraveled that the antitumor activity of ICI requires the presence of gut microbial components 19 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [19] Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This observation was confirmed in prospective trials and large meta-analyses, suggesting that gut microbiota may be instrumental for the immunostimulatory mode of action of ICI 23,24 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [23] Jin, Y. et al. The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC. J. Thorac. Oncol. 14, 1378–1389 (2019). source
- Not checked yetcites [24] Daisley, B. A. et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat. Commun. 11, 4822 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Baseline characteristics were well balanced between patients with detectable Akk (Akk + ) and undetectable Akk (Akk -) groups with respect to sex, ECOG performance status, smoking history, tumor histology, body mass index (BMI), PD-L1 expression, and line of therapy (Table S1A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plainn = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“We utilized a grid search algorithm based on the multivariable Cox model (adjusted for age, sex, ECOG performance status, ATB, histology, PD-L1 and line of treatment), with the Akaike information criterion as a performance index to determine this finest cutoff that corresponded to 4.799 (the 77 th percentile of this cohort) (Figure 2C left panel).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plainn = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“Akk overruled PD-L1 as a predictive biomarker of response to ICI in NSCLC patients.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
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In the paper
“We previously reported the stool metagenomic profiling of 100 patients diagnosed with refractory NSCLC or RCC receiving second or third line anti-PD-1 antibodies, concluding that the prevalence of A. muciniphila (Akk) was increased in patients presenting partial response or stable disease, as compared with patients in progressive disease (61 versus 34% respectively, p=0.007) 18 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
plaincorrelationaln = 100- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that the relative abundance of Akk may influence prognosis more than its absolute presence or absence.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
hedgedconditionaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“Another group performed 16S rRNA gene amplicon sequencing of 37 NSCLC patient feces, confirming that Akk was enriched in patients responding to ICI 26 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [26] Zhou, Q. et al. Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project. Nutr. Metab. 17, 90 (2020). source
plaincorrelationaln = 37- Asserted: passes — The authors put it forward as true.
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In the paper
“These results support the possibility that Akk could promote the elicitation or recirculation of Th1 cells into the tumor microenvironment, as previously shown in mouse models 18,19 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [19] Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018). source
hedgedconditionaln = 22- Asserted: passes — The authors put it forward as true.
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In the paper
“Akk was also overrepresented in patients with progression free-survival (PFS) > 3 months, when analyzing a subgroup of 60 patients with NSCLC 18 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
plaincorrelationaln = 60- Asserted: passes — The authors put it forward as true.
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In the paper
“Taken together, these results indicate that the presence of Akk is associated with important, potentially prognosis-relevant shifts in the intestinal microbiota and tumor microenvironment of NSCLC patients.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Overall, we conclude that considering the trichotomic stratification of patients into Akk -, Akk low or Akk high individuals may be a more accurate independent prognostic factor of overall survival than the dichotomic (Akk -versus Akk + ) division (likelihood ratio test of multivariable Cox models: p=0.0009).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Hence, these findings suggest that Akk and its collateral commensalism may participate in the ICI-mediated clinical benefit of patients.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on other components of the Akk -associated ecosystem
hedgedconditionaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“Confirming the clinical significance of bacterial diversity and commensals associated with responses, our results validate the growing body of evidence linking ATB use and poor clinical outcome 23,45 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [23] Jin, Y. et al. The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC. J. Thorac. Oncol. 14, 1378–1389 (2019). source
- Not checked yetcites [45] Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Second, it could not consider the interactions between the tumor mutational burden and stool Akk prevalence.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Hence, we conclude that Akk relative abundance could represent a reliable biomarker of favorable or dismal prognosis for patients receiving immunotherapy with PD-1 blockade.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
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In the paper
“The prognostic significance of this gut bacterium was validated by multivariate analyses and interaction studies indicating that Akk is markedly associated to the prognosis of advanced NSCLC treated with ICI, independently from age, gender, ECOG PS, ATB use and PD-L1.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
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In the paper
“Hence, in the context of gut injury by, or conducive to, ATB use, Akk might constitute a biomarker of ongoing but imperfect intestinal repair.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We used MCA-205 fibrosarcomas because it is normally -in SPF eubiotic mice-sensitive to anti-PD-1 Ab and has been used as a reference mouse model in our previous avatar experiments reported in 18 and 37 , both papers showing that results obtained with MCA-205 were recapitulated in orthotopic TC1 lung cancer or RENCA RENal CArcinoma models, respectively.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Pre-clinical study details:
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [37] Hwang, S. et al. Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell lung cancer. Sci. Rep. 10, 643 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, we validated in mice that Akk -stools confered resistance to PD-1 blockade.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Our study meet the pre-specified criterium of statistical significance which was set at 10% ORR increase between Akk -and Akk + patients when considering all (mostly 2L) 338 NSCLC patients (from 18.2% to 28.2% in ORR, Figure 1A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
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In the paper
“The relative abundance of Akk was associated with clinical benefit, defined by an increase in ORR and survival, taking into accounting the main microbiota-relevant confounding factors (age, gender, BMI, lines of therapy).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“High relative proportions or subdominance of A. muciniphila in the ecosystem has been associated with pathophysiological failures (such as anorexia nervosa 48 , GVHD 33 , Aging 49 , dysmetabolism 50 , HIV infection 51 , pathobionts 52 or liver injury 53 ).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [48] Depommier, C. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 1096–1103 (2019). source
- Not checked yetcites [33] Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013). source
- Not checked yetcites [49] Ouyang, J. et al. The bacterium Akkermansia muciniphila: a sentinel for gut permeability and its relevance to HIV-related inflammation. Front. Immunol. 11, 645 (2020). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Altogether, we surmise that therapeutic supplementation with a lyophilized encapsulated Akkp2261 would benefit the subgroups of patients not exposed to ATB, and devoid of endogenous Akk.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Preclinical mouse results with Akk supplementation are predictive of clinical benefit in human NSCLC patients.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Akk relative abundance represents a prognostic marker of ICI.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stratification of clinical outcome based on other components of the Akk -associated ecosystem.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 33
- Probably not a substantial claim. 20
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using shotgun metagenomic sequencing, we determined that Akk was detectable in 131 (39%) and absent in 207 (61%) patients using MetaPhlAn profiling expanded to identify the main Akk species-level genome bin (SGB9226 spp 35 , M&M Table 1).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plainn = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there was a non-statistically significant trend for older age in theAkk + group (66 years versus 64 years, p=0.08).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Akk high levels as well as ATB exposure were considered standalone variables associated with shorter OS in NSCLC patients treated with ICI.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 69 patients (20%) received antibiotics (ATB) 60 days prior to ICI initiation, with similar frequencies (p=0.68) and regimen in Akk + and Akk -groups (Table S1A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plainn = 69- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, within the Akk + group, we found significant differences in the overall microbial composition between patients with OS ≥ 12 versus OS < 12 months, but this difference was not observed in Akk -patients (Figure 2A, p=0.009 versus p=0.07).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“we found Ruminococcacae (Ruminococcus bromii, R. bicirculans, R. lactaris), Lachnospiraceae (Eubacterium siraeum, E. eligens) family members and Alistipes spp.(A.inops, A. finegoldii, A. indistinctus, A. shahii) to be enriched in Akk + stools as previously reported, 41”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Links between fecal Akk, the intestinal ecosystem and the tumor microenvironment
What the sources say
- Not checked yetcites [41] Benevides, L. et al. New insights into the diversity of the genus Faecalibacterium. Front. Microbiol. 8, 1790 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of note, for the whole cohort of patients (irrespective of the line of treatment), the median overall survival (mOS) was 18.8 months for the Akk + group compared to 15.4 months in the Akk - group (HR=0.72;(95% CI :0.73-1.62);p=0.03, Figure 1C, Table S1A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“We draw the same conclusions when using the MetaOMineR pipeline 36 (Extended Figure 2A-B”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
What the sources say
- Not checked yetcites [36] Meng, X. et al. Immune microenvironment differences between squamous and non-squamous non-small-cell lung cancer and their influence on the prognosis. Clin. Lung Cancer 20, 48–58 (2019). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Partial responses (PR), stable disease (SD) and progressive disease (PD) rates were 28%, 28% and 44%, respectively, for the Akk + group versus 18%, 31% and 50% for the Akk -group.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among ATB classes, beta-lactams were the most commonly prescribed in both groups (Table S1B, 80% in Akk + versus 64% in Akk -, p=0.33).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
plainn = 69- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with the overall microbial community showing clear separation between Akk -versus Akk low as well as between Akk low versus Akk high patients (Extended Figure 4B-C, p=0.0001 and p=0.0003, respectively).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, ATB exposure was associated with shorter OS (in univariable analysis, p=0.009 (Table S4B, Table S5), and multivariate analysis, p=0.088 (Table 1, Table S5).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FMT could confer sensitivity (when stools were Akk + ) or resistance (when stools were Akk neg) to anti-PD-1 Ab, when compared with animals in eubiosis reared in SPF conditions (without FMT).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Pre-clinical study details:
hedgeddirectn = 26- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In ATB-free subjects, Akk high patients exhibited a reduced benefit to ICI compared with Akk low individuals but not worse than the Akk neg subgroup (Figure 2G left panel).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Apart from Akk, very few bacteria (except Eubacterium hallii, Bifidobacterium adolescentis, Parasutterella excrementihominis, Intestinimonas butyriciproducens, or C. innocuum already described to mediate immunomodulatory functions [43][44][45] were also associated with prolonged (Figure 3B, Figure 3D) or reduced survival following ICI therapy (Figure 3F, Table S6)”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on other components of the Akk -associated ecosystem
What the sources say
- Not checked yetcites [43] Elkrief, A., Derosa, L., Kroemer, G., Zitvogel, L. & Routy, B. The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann. Oncol. 30, 1572–1579 (2019). source
- Not checked yetcites [44] Seo, S. W., Kim, D., Szubin, R. & Palsson, B. O. Genome-wide reconstruction of OxyR and SoxRS Transcriptional regulatory networks under oxidative stress in Escherichia coli K-12 MG1655. Cell Rep. 12, 1289–1299 (2015). source
- Not checked yetcites [45] Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011). source
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“to compare taxonomic compositional variations between Akk + versus Akk -stools in order to identify 16 bacterial species, among which 14 were positively and 2 were negatively associated with Akk fecal prevalence independently of other confounding factors such as age, gender, BMI, lines of therapy”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on other components of the Akk -associated ecosystem
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, we also observed a > 10% ORR increase between Akk -and Akk + (from 19% to 41% ORR, Figure 1B) with a mOS advantage in 1L NSCLC patients (Figure 1E).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we report that Akk was associated not only with increased alpha diversity but also with a distinct bacterial community associated with a health or immunogenic status represented by Ruminococcacae (Faecalibacterium prausnitzii, R. lactaris) and Lachnospiraceae (Dorea formicigenerans & D. longicatena, Eubacterium rectale & E. hallii, Roseburia faecis & R. intestinalis) family members”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Akkp2261 modulated the murine microbiome composition, rescuing responsiveness to PD-1 blockade.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaindirectn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“R mice harbored a relative overrepresentation of metagenomics species annotated in Figure3Ain humans harboring Akk + stools namely Intestinimonas butyriciproducens, Parasuterrella excrementihominis compared with NR mice, that in contrast, tended to be enriched in Bacteroides spp (Extended Figure6Eright panel).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recent lines of evidence point to the biological significance of the composition of the gut microbiota in influencing peripheral immune tonus and effectiveness of ICI in patients with cancer 17 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [17] Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A diverse microbiota and the presence of specific bacteria such as Akkermansia muciniphila, Ruminococcus or Bifidobacterium genera were associated with improved clinical response to ICI, correlating with increased systemic immune tonus 18,20,25 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [20] Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018). source
- Not checked yetcites [25] Santoro, A. et al. Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell. Mol. Life Sci. 75, 129–148 (2018). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The development of immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 interaction has transformed the therapeutic landscape of patients with advanced non-small cell lung cancer (NSCLC) [1][2][3][4][5][6] .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [1] Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387, 1540–1550 (2016). source
- Not checked yetcites [2] Brahmer, J. et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N. Engl. J. Med. 373, 123–135 (2015). source
- Not checked yetcites [3] Borghaei, H. et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N. Engl. J. Med. 373, 1627–1639 (2015). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Most patients with NSCLC patients develop primary or secondary resistance, or occasional rapid acceleration of the disease called “hyper-progression” 9 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [9] Riaz, N. et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171, 934–949.e16 (2017). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Landmark trials performed on previously treated patients with advanced NSCLC demonstrated superior overall survival (OS) with PD-1/PD-L1 blockade compared to standard chemotherapy [1][2][3] .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [1] Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387, 1540–1550 (2016). source
- Not checked yetcites [2] Brahmer, J. et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N. Engl. J. Med. 373, 123–135 (2015). source
- Not checked yetcites [3] Borghaei, H. et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N. Engl. J. Med. 373, 1627–1639 (2015). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence of “normal levels” of Akk in the gut (Akk low ) may be considered as a surrogate of host intestinal fitness.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The proportionality hazard assumption was questionable only for the ATB (Schoenfeld residuals trend test p=0.016),but no statistically significant interaction with time could be identified.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Stratification of clinical outcome based on the relative abundance of Akk
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, in this second independent and prospective study on 338 advanced NSCLC patients, we validated in humans using two different metagenomics pipelines as well as in mice that the presence of Akk is associated with higher ORR and longer OS in patients with NSCLC receiving ICI.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > left panel).
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In patients treated with Abiraterone acetate, an inhibitor of androgen biosynthesis approved to treat metastatic castration-resistant prostate cancer, intestinal Akk also correlated with therapeutic responses 27 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > INTRODUCTION
What the sources say
- Not checked yetcites [27] Blacher, E. et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 572, 474–480 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The intestinal residence of Akk was a proxy of richness of the gut ecosystem, as shown by the association of Akk at a relative abundance within the 77 th percentile (Akk low < 4.799%), with stool alpha diversity (Shannon diversity index).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, this study failed to investigate the functional and clinical relevance of more rare Akkermansia spp.58 different from the SGB9226 monitored in this study using MetaPhlAn 3 pipeline with a custom marker database (see Methods).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The proportionality hazard assumption was checked testing the trend of the Schoenfeld residuals with the cox.zphR function.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, it did not evaluate the predictive value of Akk in 1L chemo-immunotherapy combinations (only considering 1L IO presenting with PD-L1 >50% tumor expression).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, these results demonstrate that ATB exposure is a negative predictor of survival to ICI, associated with overabundance of Akk (Akk high ) and the relative dominance of Clostridium spp (C.bolteae, Lachnoclostridium).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > The impact of ATB use on Akk relative abundance and survival outcome
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, our study linked the gut microbiota composition to the tumor microenvironmental landscape, highlighting increased transcription of gene products of the adaptive immunity and the IFN fingerprint.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These results expand on previous observations that have been made in smaller cohorts of patients with NSCLC 18,41 and provide evidence that gut microbiome diversity and composition, specifically the relative abundance of Akk, offer relevant information to predict survival of patients with NSCLC amenable to ICI.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
- Not checked yetcites [41] Benevides, L. et al. New insights into the diversity of the genus Faecalibacterium. Front. Microbiol. 8, 1790 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All reported p-values underwent Benjamini-Hochberg two-stages False Discovery Rate (FDR) at 10%.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“These findings reconcile the results across several works, geographical distributions and sequencing technologies since Faecalibacterium, Ruminococcus and Bifidobacterium were previously reported to be enriched in North-American, Japanese and South Korean patients with melanoma and NSCLC cancers and have favorable outcome 17,20,41,44 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [17] Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018). source
- Not checked yetcites [20] Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018). source
- Not checked yetcites [41] Benevides, L. et al. New insights into the diversity of the genus Faecalibacterium. Front. Microbiol. 8, 1790 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Aside from ATB use, overabundance of Akk > 4.799 (Akk high ) was associated with a shorter overall survival than “normal” relative abundance of Akk < 4.799, possibly reflecting an underlying pathophysiological disorder of the intestinal barrier in these advanced cancer patients.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“We added further support of differentially abundant species using two different multivariate differential abundance methods; ANCOM-BC 66 and MaAsLin2 67 , that included covariates such as age, sex, BMI, cohort and sequencing batch.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Statistical analyses
What the sources say
- Not checked yetcites [66]
- Not checked yetcites [67]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the superiority hypothesis, power was set at 80% with a two-sided alpha level of 5%, using EAST® program.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Study design and treatment
plaindirectn = 292- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjustments for multiple comparisons were not made.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A recent preclinical study indicates that the anticancer effects of recombinant interleukin-2 could be improved by Akk in a Toll-like receptor-2 dependent fashion 55 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [55] Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009).
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Chi-square test P-values are two-sided, with no adjustments made for multiple comparisons (A).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaincorrelationaln = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“P-values are one-sided with no adjustment (B).”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plainn = 338- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, avatar mice transferred with Akk -human fecal material exhibited a phenotype of tumor resistance to PD-1 blockade but were rescued by Akkp2261 when Akkp2261 could shift the microbiome towards the favorable Akk associated collateral ecosystem.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Extended
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Hence, we determined that at least 292 patients-with equal distribution of 146 patients in both Akk + and Akk -groups -would be necessary to confirm our primary objective.59 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Study design and treatment
What the sources say
- Not checked yetcites [59] Fumet, J.-D. et al. Prognostic and predictive role of CD8 and PD-L1 determination in lung tumor tissue of patients under anti-PD-1 therapy. Br. J. Cancer 119, 950–960 (2018). source
plainn = 292- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Of note, the 60 patients with NSCLC already described in our previous report 18 were excluded from the principal analysis.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Human stool samples and metagenomics analyses
What the sources say
- Not checked yetcites [18] Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). source
plainn = 60- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In patients, food supplementation with Akk is safe and reduces insulinoresistance and dyslipidemia in the context of pre-diabetes 56,57 .”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > DISCUSSION
What the sources say
- Not checked yetcites [56] Li, J. et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32, 834–841 (2014). source
- Not checked yetcites [57] Nielsen, H. B. et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat. Biotechnol. 32, 822–828 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Multivariate analyses were performed using Cox regression models to determine HRs and 95% confidence intervals (CIs) for OS adjusting for other clinicopathologic features.”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
Shotgun metagenomics quantifies Akk relative abundance more precisely than 16S rRNA sequencing.
“It may be of utmost importance to risk-stratified I-O patients based on shot-gun metagenomics (rather than by 16S rRNA) sequencing to precisely quantify the relative abundance of Akk in addition to ATB use, and PD-L1 expression in prospective trials including NSCLC patients and designed to discover optimal biomarkers.”
The paper relies on this without support.
Preclinical mouse results with Akk supplementation are predictive of clinical benefit in human NSCLC patients.
“Altogether, we surmise that therapeutic supplementation with a lyophilized encapsulated Akkp2261 would benefit the subgroups of patients not exposed to ATB, and devoid of endogenous Akk.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An enrichment of SGB9226 (or SGB9228, another species of Akkermansia) beyond the 4.8% threshold (in 9% of patients), which is typically caused by antibiotic resistance and thus coincides with a dominance of the immunosuppressive Enterocloster genus and Clostridium species23,25, predicted resistance to anti-PD-(L)1 antibodies41.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Within this range, abundance of Akkermansia spp. is a surrogate marker of a healthy microbiome signature, characterized by the dominance of Lachnospiraceae and Oscillospiraceae family members41.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Intestinal dysbiosis, broadly defined as an imbalance in the composition or function of the gut microbiota, is a significant contributor to resistance against immune checkpoint inhibitor (ICI) therapies.1–16,”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [3]
In the citing paper
“our group has identified at least two distinct forms of dysbiosis, defined by either the close-to-complete absence or overabundance of Akkermansia muciniphila.3”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [3]
In the citing paper
“It should be noted that A. muciniphila B is a distinct species from A. muciniphila; although the latter was positively implicated in anti-PD-1 efficacy in NSCLC 13 (also positive in our study but not within the top 22 strains), recent analyses have revealed that it is phylogenetically and phenotypically distinct from A. muciniphila B (known as Akkermansia SGB9228 by MetaPhlAn4 taxonomy) 21 .”
From A gut microbial signature for combination immune checkpoint blockade across cancer types (2024) · cites this paper as [13]
In the citing paper
“This trichotomic distribution of Akkermansia spp. (absence, <4.8% and ≥4.8%) enables an accurate prediction of clinical benefit in patients with advanced-stage NSCLC receiving first-line or second-line anti-PD-(L)1 antibodies, independently of other clinical prognostic factors41,42.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
In the citing paper
“Together, these findings validate those obtained in preclinical avatar models involving the oral transfer of patient-derived stool samples to mice harbouring hepatocarcinomas103, sarcomas, or kidney, lung or prostate tumours28,41.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
In the citing paper
“we performed a meta-analysis and mega-analysis of stools taxonomically profiled with MetaPhlAn 4 (ref. 37) and from patients enrolled in 12 cohorts from eight published studies26,38–44 across three cancer types, and classified as responders (n = 248) or non-responders (n = 513) based on RECIST1.1 criteria response rates”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
In the citing paper
“GOMS might help to predict the efficacy of anti-PD-1 antibodies in patients with advanced-stage NSCLC, even in those with PD-L1-negative disease41.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [41]
In the citing paper
“First, correlations have been drawn across cancer indications and geographical sites between the taxonomic composition of the gut (and to some degree tumor) microbiota, and ICI responses in patients with melanoma and other cancers.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [15]
In the citing paper
“These species are often associated with poor prognosis and lack of responses to cancer immunotherapy.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [15]
In the citing paper
“avatar mice transferred with Akkermansia spp.-negative stools failed to respond to PD-1 blockade unless supplemented with oral Akkermansia spp.15”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [15]
In the citing paper
“The detectability of Akkermansia muciniphila (SGB9226 (ref.23) or SGB9228) in 56% of patients was associated with a tumor microenvironment characterized by a type 1 helper T (T H 1) cell profile (indicative of an antitumor immune response) and favorable outcome in terms of objective response rate and overall survival.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“The overabundance of Akkermansia spp.(in ~10% of patients with NSCLC), typically caused by antibiotics, correlated with a relative dominance of the immunosuppressive Enterocloster genus as well as distinct Clostridium species 23 and culminated in resistance to ICB.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“A trichotomic distribution of Akkermansia spp.abundance (absence, presence and overabundance >4.8%) enabled a more accurate prediction of clinical benefit independently of other clinical prognostic factors 22,23 than a dichotomic (absence, presence) one.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“Various F. prausnitzii SGBs are associated with favorable prognosis in patients diagnosed with several cancer types 23,24,56”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“it appears that specific strains, species or subspecies, rather than higher-level classifications (for example, genera, phyla), acquire clinical relevance as favorable or unfavorable entities 19,23,24 .”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“Plasma levels of sMAdCAM-1 (ref.39) coupled to the MGS-or PCR-based TOPOSCORE as well as prevalence and relative abundance of Akkermansia spp.23 represent useful tools to assess a potential deviation of the taxonomic composition of the intestinal ecosystem.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“The rationale of this trial is based on preclinical work demonstrating that strain p2261 is particularly efficient in stimulating anticancer immune responses in avatar mice that would otherwise not respond to ICB 22,23”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [23]
In the citing paper
“Individuals with a score falling into an intermediate category (“gray zone,” neither SIG1 nor SIG2) could be further segregated based on the relative abundance of Akkermansia spp., as previously described.”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as [31]
In the citing paper
“Normal levels of Akk (0 < Akk ≤ 4.799%, Akknorm) may be considered as a surrogate of host fitness in comparison with abnormal levels (Akk ≥ 4.8%, Akkhigh) or the absence of Akk (Akk0).”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as Derosa et al., 2022
In the citing paper
“The Akk MGSs (as well as Alistipes senegalensis and Bacteroides caccae) were not considered in this screening because their functional impact on NSCLC prognosis was trichotomic (or not significant for the two others) with no linear dose-effect relationship with patient prognosis.”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as Derosa et al., 2022
In the citing paper
“The Akkermansia muciniphila MGS was not considered in this screening because its relative abundance had a trichotomic distribution with no linear dose-effect relationship with patient prognosis as already reported in details.31”
From Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome (2024) · cites this paper as [31]
In the citing paper
“Such a high relative abundance of A. muciniphila coincided with ABX use (20% of cases) and presence of the genus Clostridium, both associated with resistance to ICI.10”
From Faecalibacterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [10]
In the citing paper
“However, higher A. muciniphila level (above 4.8% abundance) in NSCLC patients is surprisingly associated with poor survival rates.10”
From Faecalibacterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [10]
In the citing paper
“A. muciniphila is positively associated with anti-PD-1 antibodies response in NSCLC patients,2,38 and its baseline level in stool has been shown to predict this enhanced response.10”
From Faecalibacterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [10]
In the citing paper
“In the current study, we showed that high levels of F. prausnitzii in the intestinal microbiota were positively correlated with a better response to ICI in two independent cohorts of non-small cell lung cancer10 or advanced melanoma.25”
From Faecalibacterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [10]
In the citing paper
“First, antibiotic use near the start of ICB therapy is linked to worse outcomes.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
In the citing paper
“This complex community of microorganisms—including bacteria, archaea, eukaryotes, fungi, and viruses—lives in the gastrointestinal tract (Donaldson et al., 2016) and influences systemic and tumor immunity (Derosa et al., 2022; Kim et al., 2023).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
In the citing paper
“Certain bacteria are linked to favorable outcomes, including the mucin-consuming anaerobic bacterium Akkermansia muciniphila (Derosa et al., 2022; Routy et al., 2018b), Faecalibacterium prausnitzii (Gopalakrishnan et al., 2018), and Bifidobacterium spp. (Sivan et al., 2015), particularly Bifidobacterium longum (Matson et al., 2018).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
In the citing paper
“Derosa et al. (2022) demonstrated that A. muciniphila (SGB9226) exhibits a nonlinear effect on overall survival in lung and urinary tract malignancies; both its complete absence and excessively high abundance (>the 77th percentile, i.e., >4.779%) correlated with dismal overall survival in these patients.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
In the citing paper
“Some bacterial strains and species have already been found to enhance ICB efficacy.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
In the citing paper
“In preclinical studies, anti-PD-1 resistance in mice engrafted with FMT lacking A. muciniphila was reversed by its oral supplementation (Derosa et al., 2022).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Derosa et al., 2022
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
“HR=0.72”
§ Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non > Association between the presence of Akkermansia muciniphila and clinical outcome
“(95% CI :0.73-1.62)”
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192
Self-citationAdverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
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Metadata
- Authors
- Derosa, L., Routy, B., Thomas, A. M., Iebba, V., Zalcman, G., Friard, S., Mazieres, J., Audigier-Valette, C., Moro-Sibilot, D., Goldwasser, F., Silva, C. A. C., Terrisse, S., Bonvalet, M., Scherpereel, A., Pegliasco, H., Richard, C., Ghiringhelli, F., Elkrief, A., Desilets, A., Blanc-Durand, F., Cumbo, F., Blanco, A., Boidot, R., Chevrier, S., Daillère, R., Kroemer, G., Alla, L., Pons, N., Le Chatelier, E., Galleron, N., Roume, H., Dubuisson, A., Bouchard, N., Messaoudene, M., Drubay, D., Deutsch, E., Barlesi, F., Planchard, D., Segata, N., Martinez, S., Zitvogel, L., Soria, J.-C., & Besse, B.
- Affiliations
- Inserm (FR)
- Centre Hospitalier de l’Université de Montréal (CA)
- University of Trento (IT)
- University of Trieste (IT)
- Hôpital Foch (FR)
- Sorbonne Paris Cité (FR)
- Institut Gustave Roussy (FR)
- Université de Lille (FR)
- Hôpital Européen (FR)
- Centre Georges François Leclerc (FR)
- Université Paris-Saclay (FR)
- Centre Hospitalier Universitaire de Sherbrooke (CA)
- Centre Hospitalier Intercommunal Aix-Pertuis (FR)
- Corresponding author
- Zitvogel, Laurence
- ORCID
- Derosa, Lisa
- Routy, Bertrand
- Thomas, Andrew Maltez
- Iebba, Valerio
- Zalcman, Gerard
- Mazieres, Julien
- Audigier-Valette, Clarisse
- Moro-Sibilot, Denis
- Goldwasser, François
- Silva, Carolina Alves Costa
- Terrisse, Safae
- Bonvalet, Melodie
- Scherpereel, Arnaud
- Richard, Corentin
- Ghiringhelli, François
- Elkrief, Arielle
- Desilets, Antoine
- Cumbo, Fabio
- Blanco, Aitor
- Boidot, Romain
- Chevrier, Sandy
- Daillère, Romain
- Kroemer, Guido
- Alla, Laurie
- Pons, Nicolas
- Le Chatelier, Emmanuelle
- Galleron, Nathalie
- Roume, Hugo
- Dubuisson, Agathe
- Bouchard, Nicole
- Messaoudene, Meriem
- Drubay, Damien
- Deutsch, Eric
- Planchard, David
- Segata, Nicola
- Zitvogel, Laurence
- Soria, Jean-Charles
- Besse, Benjamin
- Venue
- Nature Medicine
- Published
- 2022-02
- Volume
- 28
- Issue
- 2
- Pages
- 315-324
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC9330544
- OpenAlex
- W4210773546
- Cited by
- 685
- References
- 65
- Citations by year
- 2026: 146 · 2025: 187 · 2024: 151 · 2023: 148 · 2022: 52
- FWCI
- 56.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Cancer Prevention and Research Institute of Texas (RP170067)
- Celgene
- Association pour la Recherche sur le Cancer
- Taiho Pharmaceutical
- Novocure
- Seerave Foundation
- E-Rare
- Relay Therapeutics
- European Commission (716575, 825410, 818368)
- Agence Nationale de la Recherche (2017-, ANR-10-LABX-0015, ANR-18-IBHU-0002, ANR-19-CE15-0029, ANR18, ANR-11-DPBS-0001, E-Rare-2, ANR-16-RHUS-0008)
- Fondation Leducq
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Ministero dell’Istruzione, dell’Università e della Ricerca (H2020, RBFR13EWWI_001)
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Institut Universitaire de France
- Institut National Du Cancer (19-CE15-0029-01, DGOS-Inserm_12551)
- Institut Gustave-Roussy
- Direction Générale de l’offre de Soins
- Chancellerie des Universités de Paris
- Servier
- Fondation Gustave Roussy
- Symphogen
- Da Volterra
- Institut Du Cancer de Montréal
- National Institutes of Health (RP170067, 1u01ca230551-01a1, 1U01CA230551)
- Genentech
- Samsung
- Horizon 2020 Framework Programme (MASTER-818368, OncoBiome 825410, 818368, 825410)
- Canadian Institutes of Health Research
- Labex Immuno-Oncology
- National Cancer Institute (1U01CA230551, U01 CA230551, R01CA230551)
- Institute of Cancer Research
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- Akkermansia muciniphila, non-small cell lung cancer, anti-PD-1 therapy, immune checkpoint inhibitors, predictive biomarkers, gut microbiota, PD-L1 expression, antibiotic use, Clostridium, tumor microenvironment, Eubacterium hallii, Bifidobacterium adolescentis, objective response rate, overall survival, patient stratification
- MeSH terms
- Akkermansia, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Retrospective Studies, Tumor Microenvironment, B7-H1 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-05, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-05 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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