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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“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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In the paper
“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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In the paper
“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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In the paper
“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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In the paper
“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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- It may state two separate claims as one. 33
- Probably not a substantial claim. 20
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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.
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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.
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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.
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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.
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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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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.
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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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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.
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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.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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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.
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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
“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.
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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.
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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.
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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.
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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.
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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.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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.
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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.
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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.
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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.
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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.
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- 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)”
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“33,49 This inhibition could be a result of the fact that broad-spectrum antibiotics also affect the healthy microbiota essential for optimum ICIs ef fi cacy at the same time.”
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“5 months when absent from the gastrointestinal tract) (63).”
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“The very large majority of studies were retrospective analyses of patient medical records (some of which were entered into prospectively-maintained databases); only 6 studies reported prospective observational clinical trial data (13, 43, 81, 101, 110, 114).”
BackgroundSelf-citationFaecalibacterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors
Bredon, M., Danne, C., Pham, H. P., Ruffié, P., Bessede, A., Rolhion, N., Creusot, L., Brot, L., Alonso, I., Langella, P., et al. (2024) · OncoImmunology · doi:10.1080/2162402x.2024.2374954 · Cited by 74
“In the current study, we reanalyzed two large datasets of patients treated with ICI for NSCLC 10 or advanced melanoma 25 and showed in these two independent cohorts that a high abundance of F. prausnitzii at baseline was predictive of a positive response to ICI therapy.”
InfluentialSelf-citationLandscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila
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Gut microbiome-mediated health effects of fiber and polyphenol-rich dietary interventions
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Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response
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“Is treatment with antibiotic before immunotherapy detrimental or beneficial [14, 198, 200]?”
BackgroundElkrief, A., Méndez-Salazar, E. O., Maillou, J., Vanderbilt, C. M., Gogia, P., Desilets, A., Messaoudene, M., Kelly, D., Ladanyi, M., Hellmann, M. D., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00630-w · Cited by 68
“More recently, the presence of A. muciniphila was validated as a biomarker for IO bene fi t in a prospective clinical study 12 .”
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The role of the gut microbiota in tumor, immunity, and immunotherapy
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“Additionally, intestinal A.muciniphila has emerged as a potential prognostic biomarker for PD-1 inhibitors in mNSCLC patients, showing associations with improved ORR and OS, and exhibiting a predictive value superior to PD-L1 expression in a multivariate analysis (148).”
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Genetic Engineering of Resident Bacteria in the Gut Microbiome
Arnold, J. H., Glazier, J., & Mimee, M. (2023) · Journal of Bacteriology · doi:10.1128/jb.00127-23 · Cited by 64
“An increased relative abundance of specific bacterial species, such as Bifidobacterium or Akkermansia, has been associated with successful anti-PD-1 treatment (88, 90).”
BackgroundFerrari, V., Cascio, A. L., Melacarne, A., Tanasković, N., Mozzarelli, A. M., Tiraboschi, L., Lizier, M., Salvi, M., Braga, D., Algieri, F., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.08.014 · Cited by 66
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“Its abundance is inversely correlated with IBD, metabolic disorders, and neurodegenerative disorders, but positively correlated with responses to immune checkpoint inhibitors in cancer immunotherapy [29, 43].”
A Cardiolipin from Muribaculum intestinale Induces Antigen-Specific Cytokine Responses
Bang, S., Shin, Y., Ma, X., Park, S., Graham, D. B., Xavier, R. J., & Clardy, J. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c09734 · Cited by 60
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“Studies note a correlation between Akk abundance in patients’ gastrointestinal tracts and response to immune checkpoint inhibitors (ICI) [67], with different structural variants of Akk’s glycosyltransferases potentially impacting therapy outcomes in melanoma patients [68].”
Wu, X., Fan, Y., Chung, K. P. S., Leung, C. O. N., Leung, R. W. H., So, K. K. H., Lei, M. M. L., Chau, W. K., Tong, M., Yu, J. Q., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101900 · Cited by 66
Antigen-presenting cells as specialized drivers of intestinal T cell functions
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“Among these gut microorganisms, Akkermansia muciniphila (Akk), has emerged as a potential hallmark of clinical benefit to ICI [104], and FMT combined with ICIs changes intestinal flora and improves tumor microenvironment to overcome ICIs resistance [105].”
BackgroundWang, W., Li, N., Xu, H., Wei, S., Li, Y., Ou, J., Hao, J., Zhang, J., Dong, L., Qiu, Y., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-01933-9 · Cited by 60
“Numerous studies have shown the potential benefits of A. mucin-iphila in obesity, type 2 diabetes and anti-tumour immunotherapy, and currently, there are several clinical trials involving A. muciniphila supplementation 32,33 .”
Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy
Zhu, D., Pan, W. X., Li, H., Hua, J., Zhang, C., & Zhao, K. (2025) · ACS Nano · doi:10.1021/acsnano.4c15237 · Cited by 56
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“Notably, an overabundance of A. muciniphila was previously associated with resistance to ICIs and was highlighted as an indirect sign of dysbiosis (as observed in patients with a history of antibiotic exposure) 24,27 .”
InfluentialSelf-citationXue, W., Qiu, K., Dong, B., Guo, D., Fu, J., Zhu, C., & Niu, Z. (2023) · Cancer Cell International · doi:10.1186/s12935-023-03065-8 · Cited by 55
Microbiome bacterial influencers of host immunity and response to immunotherapy
Yousefi, Y., Baines, K. J., & Vareki, S. M. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101487 · Cited by 60
The human microbiome in clinical translation: from bench to bedside
Bautista, J., Echeverría, C. E., Maldonado-Noboa, I., Ojeda-Mosquera, S., Hidalgo-Tinoco, C., & López-Cortés, A. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1632435 · Cited by 55
The gut dysbiosis-cancer axis: illuminating novel insights and implications for clinical practice
Asseri, A. H., Bakhsh, T., Abuzahrah, S. S., Ali, S., & Rather, I. A. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1208044 · Cited by 57
“Modulating the gut microbiota has emerged as a potential strategy to enhance ICI response of patients with non-small cell lung carcinoma (Derosa et al., 2022).”
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“Additionally, it was found that a “normal” relative abundance of intestinal Akkermansia in NSCLC patients was associated to better response to anti-PD1 immunotherapy, while its over-abundance was linked with a worse overall survival [104].”
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“[19] Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, Friard S, et al.”
BackgroundAkkermansia muciniphila: A potential target and pending issues for oncotherapy
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Neoadjuvant Immunotherapy: Leveraging the Immune System to Treat Early-Stage Disease
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Self-citationBodywide ecological interventions on cancer
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Self-citationMicrobiota-derived metabolites: Key modulators of cancer immunotherapies
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Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer
Zhou, K., Li, S., Zhao, Y., & Cheng, K. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1127071 · Cited by 49
“The efficacy of ICIs in epithelial tumors was correlated with the abundance of Akkermansia muciniphila (AKK) (179), and the study in advanced NSCLC conquered the conclusion (177).”
Background
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
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