The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti–Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC
Open accessAbstract
INTRODUCTION Gut microbiome affecting the responses to immune checkpoint inhibitors against advanced NSCLC has been investigated in the Western population. However, considering pre-existing genetic and gut microbiota variation, the relevance remains unknown in the East-Asian NSCLC population. This study is designed to explore the relationship between gut microbiome and clinical outcomes in Chinese patients with NSCLC who have received treatment using an anti-programmed death 1 (PD-1) blockade. METHODS Thirty-seven patients with advanced NSCLC receiving treatment with nivolumab were enrolled in CheckMate 078 (NCT02613507) and CheckMate 870 (NCT03195491). Fecal samples were collected at the starting point, when patients received nivolumab, at clinical evaluation, and when disease progression was noted. 16S ribosome RNA gene sequencing was applied to assess gut microbiota profiles. Peripheral immune signatures were determined by multicolor flow cytometry in parallel. RESULTS When subgrouping patients into responder (R) and nonresponder according to the clinical response assessed using Response Evaluation Criteria in Solid Tumor version 1.1, R patients harbored higher diversity of gut microbiome at the starting point with stable composition during the treatment. Patients with high microbiome diversity had significantly prolonged progression-free survival when compared to those with low diversity. Compositional difference was observed between the two groups as well with the enrich…
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- Premisecitation
Gut microbiota modulates immune responses in a global way including antitumor immunity.
“It is widely accepted that gut microbiota modulates immune responses in a global way including antitumor immunity.36,37”
Quote in the paperSubstantial claim1 of 2 sources checked - Findingown data
Percentages of total NK cells were positively correlated with the Shannon index.
“The percentages of total NK cells and PD-1 þ GZMB þ NK cells were also positively correlated with the Shannon index.”
Quote in the paperNot a substantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
CD45RO+CD8+ Tm cells expressing Ki-67, TIM-3, and ICOS were statistically related to the Shannon index.
“In addition, CD45RO þ CD8 þ Tm cells expressing specific markers such as Ki-67, TIM-3, and ICOS were statistically related to the Shannon index as well.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
GZMB+CD45RO+CD27-CD8+ T cells (GZMB+CD8+Tem) were positively correlated with the Shannon index.
“In T cells, functional subsets such as GZMB þ CD45RO þ CD27 þ CD8 þ T cells (GZMB þ CD8 þ Tcm); GZMB þ CD45RO þ CD27 -CD8 þ T cells (GZMB þ CD8 þ Tem) were positively correlated with the Shannon index.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Percentages of CD8+ Tcm were significantly elevated in the high-diversity group compared to the low-diversity group.
“When we compared the relevant immune signature levels between high-diversity and low-diversity groups, it was shown that the percentages of GZMB þ CD8 þ Tm, Ki67 þ CD8 þ Tm, and CD8 þ Tcm in the periphery were significantly elevated in high-diversity group.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
At the genus level, seven gut bacteria had differential abundance between responders and nonresponders at baseline (p<0.05 for all genera).
“At the genus level, we identified seven gut bacteria with differential abundance between R and NR at baseline (p < 0.05 for all genera) (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Percentages of Ki67+CD8+ Tm were significantly elevated in the high-diversity group compared to the low-diversity group.
“When we compared the relevant immune signature levels between high-diversity and low-diversity groups, it was shown that the percentages of GZMB þ CD8 þ Tm, Ki67 þ CD8 þ Tm, and CD8 þ Tcm in the periphery were significantly elevated in high-diversity group.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Shannon diversity index remained stable from baseline to different assessment timepoints (T1-T8) and progression timepoints (Kruskal-Wallis p>0.999).
“The Shannon diversity index remained stable based on Kruskal-Wallis test (p > 0.999) from baseline to different assessment timepoints (T1 to T8) as well as at progression timepoints (Fig. 4A, left).”
Quote in the paperSubstantial claim - Findingown data
Baseline samples clustered by response status (responder vs nonresponder) in PCoA.
“As shown in Figure 2D, baseline samples were clustered by response status of R and NR, respectively.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Shigella was enriched in the responder group.
“Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Ruminococcus_unclassified was enriched in the nonresponder group (p=0.0135).
“Ruminococcus_unclassified were enriched in the NR group (p ¼ 0.0135) (Fig. 3B, upper)”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Baseline Inverse Simpson diversity index was significantly higher in responders than nonresponders among Chinese advanced NSCLC patients receiving nivolumab (p=0.0257).
“Notably, alpha diversity of gut microbiome was significantly higher in R (n ¼ 13) than that in NR (n ¼ 12) at baseline according to two independent indices including Shannon index (p ¼ 0.008) and Inverse Simpson index (p ¼ 0.0257) (Fig. 2A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Alistipes putredinis was enriched in the responder group at baseline (p=0.0437).
“Alistipes putredinis (p ¼ 0.0437) (Fig. 3B, lower), Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Shannon diversity index was positively correlated with several CD8+ T cell and NK cell signatures.
“The Shannon diversity index was positively correlated with several CD8 þ T cell and NK cell signatures (Fig. 5A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Percentages of PD-1+GZMB+ NK cells were positively correlated with the Shannon index.
“The percentages of total NK cells and PD-1 þ GZMB þ NK cells were also positively correlated with the Shannon index.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Progression-free survival was significantly prolonged in patients with high gut microbiome diversity compared to those with low diversity (median PFS 209 vs 52 days, p=0.005).
“Patients with high microbiome diversity had significantly prolonged progression-free survival when compared to those with low diversity.”
- Also stated in: § Baseline Gut Microbiota Diversity is Associated With Favorable Responses to Nivolumab · plain
“It was apparent that The PFS was significantly prolonged in patients who harbored high diversity microbiota when compared to the low-diversity group (median PFS 209 versus 52 days, p ¼ 0.005) (Fig. 2C).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Also stated in: § Baseline Gut Microbiota Diversity is Associated With Favorable Responses to Nivolumab · plain
- Findingown data
GZMB+CD45RO+CD27+CD8+ T cells (GZMB+CD8+Tcm) were positively correlated with the Shannon index.
“In T cells, functional subsets such as GZMB þ CD45RO þ CD27 þ CD8 þ T cells (GZMB þ CD8 þ Tcm); GZMB þ CD45RO þ CD27 -CD8 þ T cells (GZMB þ CD8 þ Tem) were positively correlated with the Shannon index.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Shannon index was an independent predictor for PFS in multivariate Cox analysis (HR 4.2, 95% CI 1.42-12.3, p=0.009).
“In multivariate analyses performed by Cox proportional hazard model, Shannon index was confirmed as an independent predictor for PFS (hazard ratio: 4.2) (95% confidence interval: 1.42-12.3,p ¼ 0.009) (Table 2).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Relative abundance of main bacterial phylum remained stable over time.
“Analyzing precisely, the relative abundance of main bacterial phylum remained stable over time (Fig. 4D).”
Quote in the paperSubstantial claim - Findingown data
No statistical difference at the phylum level between responders and nonresponders was observed at baseline or after baseline.
“But no statistical difference at the phylum level between R and NR was observed at baseline or after baseline (data not shown).”
Quote in the paperNot a substantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Lachnobacterium was enriched in the responder group.
“Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Percentages of GZMB+CD8+ Tm were significantly elevated in the high-diversity group compared to the low-diversity group.
“When we compared the relevant immune signature levels between high-diversity and low-diversity groups, it was shown that the percentages of GZMB þ CD8 þ Tm, Ki67 þ CD8 þ Tm, and CD8 þ Tcm in the periphery were significantly elevated in high-diversity group.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Lachnospiraceae was enriched in the responder group.
“Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Significant difference in beta diversity between responders and nonresponders was observed at baseline.
“Significant difference in beta diversity between R and NR groups was also observed at baseline.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Findingown data
Baseline Shannon diversity index was significantly higher in responders than nonresponders among Chinese advanced NSCLC patients receiving nivolumab (p=0.008).
“R patients harbored higher diversity of gut microbiome at the starting point with stable composition during the treatment.”
- Also stated in: § Baseline Gut Microbiota Diversity is Associated With Favorable Responses to Nivolumab · plain
“Notably, alpha diversity of gut microbiome was significantly higher in R (n ¼ 13) than that in NR (n ¼ 12) at baseline according to two independent indices including Shannon index (p ¼ 0.008) and Inverse Simpson index (p ¼ 0.0257) (Fig. 2A).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Also stated in: § Baseline Gut Microbiota Diversity is Associated With Favorable Responses to Nivolumab · plain
- Findingown data
Among multiple immune signatures, the frequency and function of memory CD8+ T cells are mostly dedicated.
“Among multiple signatures, the frequency and function of memory CD8 þ T cells are mostly dedicated.”
Quote in the paperSubstantial claim - Findingown data
Alistipes putredinis was enriched in responders.
“Ruminococcus_unclassified was enriched in NR whereas Bifidobacterium longum, Prevotella copri, and Alistipes putredinis were enriched in R.”
Quote in the paperNot a substantial claim - Findingown data
Memory T cell profiles at baseline are similar between smoking and nonsmoking patients in this study.
“In our study, memory T cell profiles at baseline are similar between smoking and nonsmoking patients (Supplementary Fig. 4).”
Quote in the paperSubstantial claim - Findingown data
The responder/nonresponder ratio with or without antibiotic usage was similar.
“However, the R/NR ratio with or without ATB usage was similar (Table 1).”
Quote in the paperSubstantial claim - Findingown data
Smoking is the only clinical factor associated with responses to nivolumab in this study.
“Therefore, smoking is the only clinical factor associated with the responses to nivolumab in our study.”
Quote in the paperSubstantial claim - Findingown data
Seven genera were identified as different between responders and nonresponders.
“In our study, seven genera were identified different between R and NR.”
Quote in the paperSubstantial claim - Findingown data
There was no difference in the interval from last chemotherapy to first nivolumab infusion between R and NR groups.
“There was no difference in the interval from the date of last chemotherapy to that of first nivolumab infusion between R and NR groups (Supplementary Fig. 5, left).”
Quote in the paperNot a substantial claim - Findingown data
Bifidobacterium longum was enriched in responders.
“Ruminococcus_unclassified was enriched in NR whereas Bifidobacterium longum, Prevotella copri, and Alistipes putredinis were enriched in R.”
Quote in the paperSubstantial claim - Findingown data
Prevotella copri was enriched in responders.
“Ruminococcus_unclassified was enriched in NR whereas Bifidobacterium longum, Prevotella copri, and Alistipes putredinis were enriched in R.”
Quote in the paperSubstantial claim - Findingown data
The functional subset of CD8+ T cells with Granzyme B production is positively correlated with the diversity index.
“the functional subset with Granzyme B production is also positively correlated with the diversity index”
Quote in the paperSubstantial claim - Findingown data
Gut microbiota composition differed between responders and nonresponders at baseline (p=0.001).
“Principal coordinates analysis of gut microbiota at baseline.Red legends represented NR and blue legends represented R. Statistical analysis was performed by multivariate analysis of variance test.p ¼ 0.001.”
Quote in the paperSubstantial claim - Findingown data
Smoking status was associated with PFS in univariate and multivariate analyses (HR 0.30, 95% CI 0.11-0.86, p=0.025).
“| Smoking status | Smoker vs. Nonsmoker | 6.0(1.8-10.3) vs. 1.5(1.2-1.8) | 0.016 | 0.025 | 0.30(0.11-0.86) |”
Quote in the paperNot a substantial claim - Findingown data
Baseline gut microbiota composition was similar between participants with and without antibiotics before first nivolumab infusion.
“The composition of gut microbiota at baseline between participants with or without ATB before first nivolumab infusion was similar (Supplementary Fig. 2)”
Quote in the paperSubstantial claim - Findingown data
Ruminococcus_unclassified was enriched in nonresponders.
“Ruminococcus_unclassified was enriched in NR whereas Bifidobacterium longum, Prevotella copri, and Alistipes putredinis were enriched in R.”
Quote in the paperNot a substantial claim - Findingown data
Most bacteria enriched in responders in this study belong to pro-inflammatory gram-negative bacteria.
“More interestingly, most bacteria enriched in R in our study belong to pro-inflammatory gram-negative bacteria.”
Quote in the paperNot a substantial claim - Findingown data
In multivariate analysis, low alpha-diversity (Shannon index) was associated with shorter PFS compared with high alpha-diversity (HR 4.2, 95% CI 1.42-12.3, p=0.009).
“| Alpha-diversity (Shannon index) | Low vs. high | 1.7(1.3-2.1) vs. 7.0(3.3-10.6) | 0.005 | 0.009 | 4.2(1.42-12.3) |”
Quote in the paperSubstantial claim - Findingown data
Gut microbiota profiles remain stable during treatment.
“Gut microbiota profiles remain stable during the treatment.”
Quote in the paperNot a substantial claim - Findingown data
Gut microbiota remained stable in longitudinal samples within one individual.
“We also observed that gut microbiota remained stable in longitudinal samples within one individual in our study.”
Quote in the paperNot a substantial claim - Findingown data
Smoking status differed between responders and nonresponders (p=0.008).
“| Smoker | 26 | 20(87.0) | 6(42.9) | 0.008 |”
Quote in the paperNot a substantial claim - Findingown data
Shannon diversity index correlates with peripheral immune signatures (memory CD8+ T cell subsets and NK cell subsets).
“Correlation analysis of Shannon diversity index with peripheral immune signatures.”
Quote in the paperSubstantial claim - Findingown data
Among all clinical manifestations, smoking is the only factor that affects responses to nivolumab treatment in this study.
“Among all the clinical manifestations, smoking is the only factor that affects the responses to nivolumab treatment in our study.”
Quote in the paperNot a substantial claim - Findingown data
The diversity of gut microbiota is associated with favorable response to nivolumab therapy against NSCLC in Chinese cohorts.
“Our study shows that the diversity of gut microbiota is associated with favorable response to nivolumab therapy against NSCLC in Chinese cohorts.”
Quote in the paperSubstantial claim - Findingown data
Antibiotic usage did not differ between responders and nonresponders (p=0.713).
“| Yes | 11 | 6(26.1) | 5(35.7) | 0.713 |”
Quote in the paperNot a substantial claim - Findingown data
Gut microbiota diversity was irrelevant to the time-off of chemotherapy in this cohort.
“Correlation analysis showed that the diversity of gut microbiota was irrelevant to the time-off of chemotherapy in our cohort study as well (Supplementary Fig. 5, right).”
Quote in the paperNot a substantial claim - Findingown data
Seven bacterial genera had statistically differential abundance in responders and nonresponders at baseline.
“Heatmap of seven bacterial genera with statistically differential abundance in R (n ¼ 13) and NR (n ¼ 12) at baseline.”
Quote in the paperSubstantial claim - Findingown data
Median PFS was similar between ATB-treated and ATB-naïve patients.
“Median PFS was similar between ATB-treated and -naïve patients (median PFS: 126 days versus 117.9 days, p > 0.05)”
Quote in the paperNot a substantial claim - Interpretationown data
The influence of gut microbiome on anti-PD-1 treatment is probably owing to modulating memory T cell responses and NK cell function.
“Our results thus imply that the influence of gut microbiome on anti-PD-1 treatment is probably owing to modulating memory T cell responses and NK cell function.”
Quote in the paperSubstantial claim - Interpretationown data
Nivolumab treatment does not modify gut microbiome community in patients with advanced NSCLC.
“Altogether, these data indicate that nivolumab treatment does not modify gut microbiome community in patients with advanced NSCLC.”
Quote in the paperSubstantial claim - Interpretationown data
The association between gut microbiome diversity and systematic immune signatures highlights memory CD8+ T cells and NK cells as potential mediators of antitumor immunity upon ICI treatment.
“In addition, the association between gut microbiome diversity and systematic immune signatures highlights memory CD8 þ T cells and NK cells as potential mediators of antitumor immunity upon ICI treatment.”
Quote in the paperSubstantial claim - Interpretationreasoning
Regardless of genetic background and geographic location with different lifestyles and diet styles, the diversity of gut microbiota might be a common benefit factor to ICI treatment.
“Our results thus show that regardless of genetic background and geographic location with different lifestyles and diet styles, the diversity of gut microbiota might be a common benefit factor to ICI treatment.”
Quote in the paperSubstantial claim - Premisecitation
Gut microbiome structures are remarkably variable among different races and ethnicities.
“Gut microbiome structures have been elucidated remarkably variable among different races and ethnicities.24”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] He, 2018, Regional variation limits applications of healthy gut microbiome reference ranges and disease models, Nat Med source
- Interpretationown data
There exist strong associations between the diversity of gut microbial content and certain systematic immune signatures.
“Therefore, there exists the strong associations between the diversity of gut microbial content and certain systematic immune signatures.”
Quote in the paperSubstantial claim - Interpretationown data
The positive correlation between Granzyme B production and diversity index can partially explain why patients with high microbiota diversity respond better to ICI therapy.
“which can partially explain why patients with high microbiota diversity respond better to ICI therapy.”
Quote in the paperSubstantial claim - Interpretationown data
Memory T cells are more likely affected by gut microbiota rather than other factors such as smoking.
“This result confers that memory T cells are more likely affected by gut microbiota rather than other factors such as smoking.”
Quote in the paperSubstantial claim - Interpretationreasoning
Systemic antitumor immune responses are diverse in patients with different gut microbiome composition.
“it is not out of expectation that systemic antitumor immune responses are diverse in patients with different gut microbiome composition.”
Quote in the paperSubstantial claim - Interpretationreasoning
Patients with more diverse gut microbiota at baseline benefit from ICI immunotherapy to a greater extent.
“we propose that patients with more diverse gut microbiota at baseline benefit from ICI immunotherapy to a greater extent.”
Quote in the paperSubstantial claim - Interpretationreasoning
Circulating CD8+ T cell subsets reported here probably reflect the roles of gut microbiota on systemic immune responses.
“circulating CD8 þ T cell subsets reported here are probably inclined to reflect the roles of gut microbiota on systematic immune responses.”
Quote in the paperSubstantial claim - Interpretationown data
The increase in Ki67+ CD8+ Tm in patients with high microbiota diversity implies that gut microbiota modulate the proliferation of certain immune cell populations.
“The increase in Ki67 þ CD8 þ Tm in the patients with high microbiota diversity implies that gut microbiota also modulate the proliferation of certain immune cell populations.”
Quote in the paperSubstantial claim - Interpretationreasoning
The benefit from ICI immunotherapy in patients with more diverse gut microbiota might be mediated by reprogramming systemic antitumor immune responses.
“This might be mediated by reprogramming systemic antitumor immune responses.”
Quote in the paperSubstantial claim - Interpretationown data
Antibiotic use before first nivolumab infusion did not affect gut microbiota composition in this study.
“which excludes the possible effects of ATB on gut microbiota in our study.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 28
- May combine two claims. 14
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAbnormal diversity (dysbiosis) in the gut has been proven to be associated with human diseases such as obesity, inflammatory bowel disease, and cancer.
“Abnormal diversity (dysbiosis) in the gut has been proven to be associated with human diseases, such as obesity, inflammatory bowel disease, cancer, etc. 20,21,33,34”
Quote in the paperNot a substantial claim2 of 4 sources checked- cites [20] Bultman, 2014, Emerging roles of the microbiome in cancer, Carcinogenesis source
The metagenomic-studies section (page unavailable) describes dysbiosis and reports microbiome differences in Crohn’s disease; its discussion of colorectal tumors also supports an association with cancer. The obesity evidence in the cited passages concerns mice, so it does not establish the claimed association between gut dysbiosis and obesity in humans. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites [21] Wallace, 2011, Human gut microbiota and its relationship to health and disease, Nutrition Rev source
- cites [33] Herbert, 2011, Gut microbiome, obesity, and metabolic dysfunction, J Clin Invest source
- cites [34] Ni, 2017, Gut microbiota and IBD: causation or correlation?, Nat Rev Gastroenterol Hepatol source
The ‘Microbiota composition and IBD’ section documents differences in gut microbial diversity and composition between people with IBD and healthy individuals, supporting the claimed association with IBD. Our copy does not establish the corresponding associations with obesity or cancer; the cancer-related reference alone does not substantiate that broader claim. The paper also cautions that association does not prove causation, although the citing sentence claims association rather than causation. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationExtrinsic factors such as geographical location or diet and life styles, and intrinsic factors such as genetics or early-life exposures are main contributors to gut microbiome divergences among races and ethnicities.
“Extrinsic factors, such as geographical location or diet and life styles, and intrinsic factors such as genetics or early-life exposures are main contributors to such divergences.[25][26][27]”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [25] Falony, 2016, Population-level analysis of gut microbiome variation, Science source
- cites [26] Gupta, 2017, Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity, Front Microbiol source
The Summary and Gastrointestinal microbiome sections link geographic differences, diet and lifestyle to variation in gut microbiomes. They also discuss genetics, but say its role in shaping the gut microbiome is unclear; the gastrointestinal section mentions early-life exposures such as delivery mode, breastfeeding and antibiotics without establishing them as main contributors to ethnic or racial divergences. The claim is therefore stronger than this review supports. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [27] Ran, 2015, Host genetic variation impacts microbiome composition across human body sites, Genome Biol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRecent antibiotic usage in NSCLC patients was associated with shorter overall survival, although there was no difference in objective response or PFS.
“It has been reported previously that recent ATB usage in NSCLC patients was associated with shorter OS, although there was no difference in terms of objective response or PFS.32”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [32] Derosa, 2018, 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 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral clinical factors including smoking, previous treatment, and antibiotic usage are reported to be involved in affecting the efficacy of ICI therapy.
“Several clinical factors are reported to be involved in affecting the efficacy of ICI therapy, including smoking, previous treatment, and ATB usage.15,32,39”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [15] Routy, 2017, Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors, Science source
- cites [32] Derosa, 2018, 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 source
- cites [39] Garon, 2015, Pembrolizumab for the treatment of non–small-cell lung cancer, N Engl J Med source
Classified as probably not a substantial claim.
PremisecitationHigh diversity of gut microbiome favored clinical outcomes of anti-PD-1 immunotherapy in melanoma patients in the Western population.
“Recently, Gopalakrishnan et al. 35 reported that patients with a high diversity of gut microbiome favored the clinical outcomes of anti-PD-1 immunotherapy in melanoma patients in the Western population.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [35] Gopalakrishnan, 2018, Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients, Science source
The paper’s results report higher gut-microbiome alpha diversity in responders than non-responders and significantly longer progression-free survival in patients with high diversity. These findings support the clinical-outcome association, but the passages in our copy do not identify the cohort as a “Western population”; a search for that term found no such designation. (LLM, conf=0.83)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationBoth innate and adaptive immune responses can be reshaped by gut microbiome.
“Both innate and adaptive immune responses can be reshaped by gut microbiome.”
Quote in the paperSubstantial claim1 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA linear relationship has been reported between the proportion of ICI benefit and PD-L1 expression in NSCLC tumor sections.
“A linear relationship has been reported between the proportion of ICI benefit and PD-L1 expression in NSCLC tumor sections.7,8”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [7] Sacher, 2016, Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non–small-cell lung cancer: a review, JAMA Oncol source
- cites [8] Topalian, 2012, Safety, activity, and immune correlates of anti–PD-1 antibody in cancer, N Engl J Med source
The Results section (PD-L1 Expression in Tumors; page unavailable) reports objective responses in 9 of 25 patients with PD-L1–positive tumors and none of 17 with PD-L1–negative tumors. That supports an association with response to anti–PD-1 treatment, but the analysis pooled cancer types, included only 10 patients with NSCLC, and compared positive with negative specimens; it did not establish a linear relationship between expression level and benefit specifically in NSCLC. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevious studies report an association of gram-negative bacteria such as Akkermansia muciniphila, Alistipes, and Porphyromonas with better clinical response to immunotherapy.
“There are several previous studies reporting the association of gram-negative bacteria, such as Akkermansia muciniphila, Alistipes, and Porphyromonas with better clinical response to immunotherapy.14,15,36”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [14] Gopalakrishnan, 2017, Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients, Science source
The paper’s results support an association between gut bacteria and response to anti-PD-1 therapy in melanoma patients. However, the reported favorable taxa are Clostridiales, Ruminococcaceae and Faecalibacterium; the cited paper does not report a favorable association for Akkermansia muciniphila, Alistipes or Porphyromonas. It instead reports Bacteroidales enrichment in nonresponders (results, page unavailable). (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [15] Routy, 2017, Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors, Science source
- cites [36] Noriho, 2013, Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment, Science source
The passage on microbiota correlations (section labeled Abstract; page unavailable) identifies gram-negative Alistipes as positively correlated with TNF expression and reports that A. shahii restored a tumor-associated TNF response in mice given CpG-ODN. It does not establish better clinical response to immunotherapy, and the passages do not report such an association for Akkermansia muciniphila or Porphyromonas. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationResponses to ICI treatment have still been observed in those with low or undetectable levels of PD-L1 expression.
“Nevertheless, the responses to ICI treatment have still been observed in those with low or undetectable levels of PD-L1 expression.9”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [9] Robert, 2015, Nivolumab in previously untreated melanoma without BRAF mutation, N Engl J Med source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPD-L1 expression on tumor cells is regarded as the most available biomarker to predict the efficacy of ICIs in NSCLC and other malignancies.
“So far, PD-L1 expression on tumor cells is regarded as the most available biomarker to predict the efficacy of ICIs in NSCLC and other malignancies.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [7] Sacher, 2016, Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non–small-cell lung cancer: a review, JAMA Oncol source
- cites [8] Topalian, 2012, Safety, activity, and immune correlates of anti–PD-1 antibody in cancer, N Engl J Med source
The Discussion describes tumor PD-L1 expression as a candidate marker for response to anti–PD-1 therapy, and the Results report responses in 9 of 25 patients with PD-L1–positive tumors versus none of 17 with PD-L1–negative tumors. But the paper calls this analysis preliminary and says further studies are needed; it does not establish PD-L1 as the most available biomarker or address predictive efficacy across ICIs generally. Page numbers are not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationICOS and TIM3 expressions on specific T cell subsets are related to antitumor immunity.
“ICOS and TIM3 expressions on specific T cells subsets are also related to antitumor immunity.52,53”
Quote in the paperNot a substantial claim1 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevotella copri was strongly correlated with disease severity in rheumatoid arthritis.
“Prevotella copri was strongly correlated with the disease severity in rheumatoid arthritis, which is a systemic autoimmune disease with the proliferation of pro-inflammatory T cells.47”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [47] Scher, 2013, Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis, Elife source
The Results (‘Association of Prevotella with new-onset rheumatoid arthritis’; page unavailable) report that P. copri was significantly more prevalent in untreated, new-onset RA patients than in the comparison groups. The paper reports an association with disease presence, not a strong correlation between P. copri and RA severity; its Discussion notes only slightly lower DAS28 disease-activity scores in the chronic RA group. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRecent studies reported effects of PD-1 blockade on proliferation of CD8+ T cells, which is beneficial for ICI treatment.
“Recent studies already reported the effects of PD-1 blockade on the proliferation of CD8 þ T cells, which is beneficial for ICI treatment.51”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [51] Kamphorst, 2017, Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1–targeted therapy in lung cancer patients, Proc Natl Acad Sci U S A source
The Results report that PD-1–targeted therapy induced proliferation of PD-1+ CD8 T cells in patients with lung cancer. They also report an association between early proliferative responses and positive clinical outcomes, but do not establish that the proliferation itself benefits treatment; the authors call that outcome finding preliminary (Results; page not provided). (LLM, conf=0.86)
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataThe Inverse Simpson index difference between responders and nonresponders at T1 was not statistically significant, although a tendency remained.
“However, difference in Inverse Simpson index was not significant between two groups at T1, although the tendency remained (Fig. 2A).”
Quote in the paperNot a substantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
May combine two claims.
Findingown dataPaired samples at baseline and T1 or baseline and progression displayed no differences in Shannon index (Wilcoxon p>0.05).
“Paired samples at baseline and at the T1 (Fig. 4A, middle) or baseline and progression timepoint (Fig. 4A, right) displayed no differences in Shannon index based on Wilcoxon matched-pairs signed rank test (p > 0.05).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBifidobacterium longum was enriched in the responder group at baseline (p=0.0303) and at T1 (p=0.0397).
“Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
- Also stated in: § Compositional Difference in Gut Microbiome in Response to Nivolumab · plain
“Two bacteria, Bifidobacterium longum and Prevotella copri, were enriched in the R group both at baseline (p ¼ 0.0303 and p ¼ 0.0093, respectively) and T1 time point (p ¼ 0.0397 and p ¼ 0.0426, respectively) (Fig. 3C).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Also stated in: § Compositional Difference in Gut Microbiome in Response to Nivolumab · plain
May combine two claims.
Findingown dataPrevotella copri was enriched in the responder group at baseline (p=0.0093) and at T1 (p=0.0426).
“Prevotella copri, Bifidobacterium longum, Lachnobacterium, Lachnospiraceae, and Shigella were enriched in R (Fig. 3A).”
- Also stated in: § Compositional Difference in Gut Microbiome in Response to Nivolumab · plain
“Two bacteria, Bifidobacterium longum and Prevotella copri, were enriched in the R group both at baseline (p ¼ 0.0303 and p ¼ 0.0093, respectively) and T1 time point (p ¼ 0.0397 and p ¼ 0.0426, respectively) (Fig. 3C).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
- Also stated in: § Compositional Difference in Gut Microbiome in Response to Nivolumab · plain
May combine two claims.
Findingown dataIn longitudinal PCoA, gut microbiota from one patient at different sampling timepoints clustered well, and responder and nonresponder individuals were separated clearly.
“While gut microbiota from one patient at different sampling timepoints (represented by one shape) were clustered very well, R and NR individuals were separated clearly as well (pink and purple circles) (Fig. 4C).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataThe Shannon index at T1 was significantly higher in responders than nonresponders (p=0.0301).
“The increase of Shannon index at the T1 timepoint in R was consistent with that at baseline (p ¼ 0.0301).”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataComponents 1 and 2 accounted for 10.82% and 7.69% of variance in PCoA.
“Components 1 and 2 accounted for 10.82% and 7.69% of variance, respectively, in PCoA.”
Quote in the paperNot a substantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown data11 of 37 patients (29.7%) were prescribed antibiotics within 2 months.
“When we examined ATB usage in our cohort, 11 of 37 patients (29.7%) were prescribed ATB within 2 month.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo difference was observed in sex, disease history, disease stage, and treatment between responders and nonresponders except smoking history (p=0.008).
“No difference was observed in sex, disease history, disease stage, and the treatment between R and NR patients except smoking history (p ¼ 0.008).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Findingown dataBaseline fecal samples were obtained from 25 patients, 13 responders and 12 nonresponders.
“Fecal samples at baseline were obtained from 25 patients, among whom 13 patients were R and 12 patients were NR (Fig. 1).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Findingown dataTwenty-three patients were classified as responders (5 partial response, 18 stable disease) and 14 as nonresponders (disease progression).
“Twenty-three patients being evaluated as either partial response (n ¼ 5) or stable disease (n ¼ 18) were classified as R whereas the others (n ¼ 14) with disease progression after the first clinical assessment were classified as NR.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataPatients with better clinical responses exhibit higher diversity and a distinct gut microbiome composition.
“Our results indicate that patients with better clinical responses exhibit higher diversity as well as a distinct gut microbiome composition.”
Quote in the paperSubstantial claim- Rests on an assumption: The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningIn the antitumor setting, exacerbation of immune responses might assist the ability of immune surveillance in patients.
“In the antitumor setting, the exacerbation of immune responses might assist the ability of immune surveillance in the patients.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataOf 42 enrolled patients, 1 died after a single infusion, 2 were lost to follow-up, 2 discontinued due to grade 3-4 adverse events, and 37 remained for grouping.
“Among them, 1 patient died after a single infusion of nivolumab.Two patients were lost during the follow-up study.Two patients discontinued therapy because of grade 3-4 adverse events.The remaining 37 patients were grouped according to clinical assessment.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll procedures were conducted in accordance with the Declaration of Helsinki.
“All the procedures were conducted in accordance with the Declaration of Helsinki.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA latest publication introduced 11 bacterial strains from healthy donors' feces to induce interferon-g producing CD8+ T cells in the intestine, which mediates effective antitumor immunity in a mouse model.
“A latest publication has introduced 11 bacterial strains from healthy donors' feces to induce interferon-g producing CD8 þ T cells in the intestine, which mediates effective antitumor immunity in a mouse model.54”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [54] Tanoue, 2019, A defined commensal consortium elicits CD8 T cells and anti-cancer immunity, Nature source
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningModulation of gut microbiota before treatment might provide an alternative way to enhance the efficacy of ICI immunotherapy once validated in large cohort studies.
“The significance of our study lies in that the modulation of gut microbiota before the treatment might provide an alternative way to enhance the efficacy of ICI immunotherapy once validated in large cohort studies.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMedian PFS was longer in current and former smokers compared with nonsmokers in nivolumab monotherapy for first-line treatment of advanced NSCLC.
“Median PFS was longer in current and former smokers compared with nonsmokers in nivolumab monotherapy for first-line treatment of advanced NSCLC as well.44”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Gettinger, 2016, Nivolumab monotherapy for first-line treatment of advanced non–small-cell lung cancer, J Clin Oncol source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPatients who develop immune-related adverse events are more sensitive to ICI treatment.
“This is also consistent with the report that patients who develop immune-related adverse events are more sensitive to ICI treatment.48”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] Haratani, 2018, Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer, JAMA Oncol source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationOnly 20% of patients with advanced NSCLC benefit from nivolumab, whereas up to 50% experience treatment-related adverse events and grade 3-4 toxicities occur in 10% receiving nivolumab.
“However, only 20% of patients with advanced NSCLC benefit from the treatment, whereas up to 50% experience treatmentrelated adverse events in which grade 3-4 toxicities occur in 10% patients receiving nivolumab.6”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Spain, 2016, Management of toxicities of immune checkpoint inhibitors, Cancer Treat Rev source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe study was approved by the Ethics Committee of Shanghai Chest Hospital.
“The study was approved by the Ethics Committee of Shanghai Chest Hospital.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningGut microbiota becomes an intrinsic biosensor to sensitize anti-PD-1 treatment, leading to different clinical outcomes.
“Gut microbiota thus becomes an intrinsic biosensor to sensitize anti-PD-1 treatment, which in turn leads to different clinical outcomes.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNivolumab yields superior overall survival compared with docetaxel (median OS 12 mo vs 9.6 mo).
“According to results from CheckMate-078, nivolumab yields superior overall survival (OS) compared with the docetaxel arm (median OS: 12 mo versus 9.6 mo). 5”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Wu, 2019, Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: CheckMate 078 randomized phase III clinical trial, J. Thorac Oncol source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenAll patients were informed of the study and consented to enrollment.
“All patients were informed of the study and consented to the enrollment.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBifidobacterium longum could increase production of pro-inflammatory cytokine TNF-alpha and significantly improve tumor control upon anti-PD-L1 therapy in a B16.SIY tumor mouse model.
“It has been shown in another study that Bifidobacterium longum could increase the production of pro-inflammatory cytokine tumor necrosis factor-alpha and significantly improve tumor control upon anti-PD-L1 therapy in a B16.SIY tumor mouse model.46”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [46] Ayelet, 2015, Commensal bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy, Science source
The paper relies on this without support.
The baseline fecal samples available from 25 of the 37 enrolled patients are representative of the full enrolled cohort.
“Fecal samples at baseline were obtained from 25 patients, among whom 13 patients were R and 12 patients were NR (Fig. 1).”
The paper relies on this without support.
Pro-inflammatory gram-negative bacteria in the gut of older patients increase systemic chronic inflammation largely via lipopolysaccharide release.
“It is already evident that the increase of pro-inflammatory gramnegative bacteria in the gut of older patients is associated with systematic and chronic inflammation.It is largely mediated by more release of lipopolysaccharide.”
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?
Increased gut microbiome diversity is closely associated with improved responses to ICIs.
“Numerous studies have shown that increased gut microbiome diversity is closely associated with improved responses to ICIs25,123,137,138.”
From Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors (2025) · cites this paper as [25]
The diversity of gut microbiota in patients with lung cancer is positively correlated with the efficacy of immunotherapy.
“the diversity of gut microbiota in patients with lung cancer was positively correlated with the efficacy of immunotherapy (25,26).”
From The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy (2021) · cites this paper as [25]
Prospective trials and large meta-analyses support the idea that gut microbiota may be important for the immunostimulatory action of immune checkpoint inhibitors.
“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 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [23]
The results validate the growing body of evidence linking antibiotic use and poor clinical outcome.
“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 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [23]
In previous baseline studies, P. copri has been associated with ICB response.
“In previous baseline studies, P. copri has been associated with ICB response26,27.”
From Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma (2024) · cites this paper as [27]
Germline genetic variations and microbiome differences between individuals are likely to influence therapeutic responses and immune-related adverse effects.
“Additionally, germline genetic variations389–392 and microbiome differences between individuals359,393–395 are likely to influence therapeutic responses and immune-related adverse effects.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [395]
In Chinese advanced NSCLC patients receiving nivolumab, Alistipes putredinis, Bifidobacterium longum and Prevotella copri were enriched in responding patients, whereas Ruminococcus_unclassified was enriched in non-responding patients.
“Jin et al enrolled 37 Chinese advanced NSCLC patients receiving nivolumab and patients using second-generation sequencing, found an enrichment of Alistipes putredinis, Bifidobacterium longum and Prevotella copri in responding patients, whereas Ruminococcus_unclassified was enriched in non-responding patients.51”
Antibiotics treatment altered the intestinal microbiota at a family level, followed by reduced cytotoxic NK cells and increased growth of intracranial glioma, suggesting that an abundant microbiome facilitated the accumulation of NK cells and enhanced tumor surveillance.
“Conversely, antibiotics treatment altered the intestinal microbiota at a family level, followed by reduced cytotoxic NK cells and increased growth of intracranial glioma, suggesting that an abundant microbiome facilitated the accumulation of NK cells and enhanced tumor surveillance [29].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [29]
A. muciniphila is positively associated with anti-PD-1 antibody response in NSCLC patients, and its baseline level in stool has been shown to predict this enhanced response.
“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 <i>Faecalibacterium prausnitzii</i> strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [38]
Responding patients harbored higher diversity and stable composition of innate gut microbiome during treatment and also had significantly prolonged PFS.
“According to their results, responding patients harbored higher diversity and stable composition of innate gut microbiome during treatment and also had significantly prolonged PFS.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [58]
Alistipes putredinis, Bifidobacterium longum, and Prevotella copri were enriched in responders, whereas Ruminococcus_unclassified was found mainly in non-responding patients.
“In detail, Alistipes putredinis, Bifidobacterium longum, and Prevotella copri were enriched in responders, whereas Ruminococcus_unclassified was found mainly in non-responding patients.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [58]
A greater frequency of memory CD8+ T cell and natural killer cell subgroups was observed in the periphery blood of responding patients.
“As expected, a greater frequency of memory CD8+ T cell and natural killer cell subgroups was also observed in the periphery blood of responding patients.”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [58]
In Chinese patients with advanced non-small-cell lung carcinoma, higher diversity of gut microbiota is associated with better response to anti-PD-1 immunotherapy.
“In Chinese patients with advanced non-small-cell lung carcinoma, the higher was the diversity of the gut microbiota, the better was the response observed to anti-PD-1 immunotherapy (58).”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [58]
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.
Responder EGFR-negative percentage is incorrect
MinorTwenty-two of 23 responders were EGFR-mutation negative, or about 95.7%, not 99.6%.
Reported 99.6 · recomputed 95.652174
“| No | 33 | 22(99.6) | 11(78.6) | |”
Responder male percentage is incorrect
MinorThere were 20 male responders among 23 responders, or about 87.0%, not 70.0%.
Reported 70 · recomputed 86.956522
“| Male | 29 | 20(70.0) | 9(69.2) | 0.215 |”
Nonresponder female percentage is incorrect
MinorFive of 14 nonresponders were female, or about 35.7%, not 30.7%.
Reported 30.7 · recomputed 35.714286
“| Female | 8 | 3(30.0) | 5(30.7) | |”
Enrollment count differs between abstract and results
MinorThe abstract says 37 patients were enrolled, whereas the results say 42 were enrolled and that 37 remained after exclusions.
“Methods: Thirty-seven patients with advanced NSCLC receiving treatment with nivolumab were enrolled in CheckMate 078 (NCT02613507) and CheckMate 870 (NCT03195491).”
“Forty-two Chinese patients with advanced NSCLC were consented and enrolled.”
Nonresponder male percentage is incorrect
MinorNine of 14 nonresponders were male, or about 64.3%, not 69.2%.
Reported 69.2 · recomputed 64.285714
“| Male | 29 | 20(70.0) | 9(69.2) | 0.215 |”
Responder squamous-histology percentage is incorrect
MinorNine of 23 responders had squamous histology, or about 39.1%, not 29.1%.
Reported 29.1 · recomputed 39.130435
“| Squamous | 15 | 9(29.1) | 6(42.9) | >0.999 |”
Nonresponder stage III percentage uses the wrong scale
MinorOne of 14 nonresponders had stage III disease, or about 7.1%. The reported 0.07 resembles a fraction rather than a percentage, unlike the adjacent percentages.
Reported 0.07 · recomputed 7.142857
“| III | 6 | 5(21.7) | 1(0.07) | 0.376 |”
Responder female percentage is incorrect
MinorThree of 23 responders were female, or about 13.0%, not 30.0%.
Reported 30 · recomputed 13.043478
“| Female | 8 | 3(30.0) | 5(30.7) | |”
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- Gopalakrishnan, 2018, Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients, Science, 359, 97, 10.1126/science.aan4236 · DOI · Paper page
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“Data from 37 advanced NSCLC patients receiving nivolumab enrolled in clinical trials have demonstrated a strong correlation between the level of gut microbiome diversity and anti-PD-1 antibody efficacy in advanced NSCLC Chinese patients (Jin et al., 2019).”
BackgroundGut microbiome, big data and machine learning to promote precision medicine for cancer
Cammarota, G., Ianiro, G., Ahern, A., Carbone, C., Temko, A., Claesson, M. J., Gasbarrini, A., & Tortora, G. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0327-3 · Cited by 324 · see citing works
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“Urothelial cancer Atezolizumab TMB [73]”
The Gut Microbiota and Respiratory Diseases: New Evidence
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“…non-small-cell lung cancer (NSCLC) who responded to antiprogrammed death 1 (PD-1) immunotherapy (responders) harbored a higher gut microbial diversity than those who did not respond (nonresponders), and gut microbial diversity was positively associated with progression-free survival (PFS) [75].”
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“longum, and Prevotella copri.(459) Similarly, the gut microbiome potentially exerts a profound effect on the responses of HCC patients receiving antiPD-1 mAb.”
BackgroundThe cutting-edge progress of immune-checkpoint blockade in lung cancer
Zhou, F., Qiao, M., & Zhou, C. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00577-5 · Cited by 235 · see citing works
Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy
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“Improving T cell infiltration in the tumor via manipulating gut microbiota is an area of active research, which yet still stays at its infant stage [57].”
BackgroundCancer immunotherapy: it’s time to better predict patients’ response
Pilard, C., Ancion, M., Delvenne, P., Jérusalem, G., Hubert, P., & Herfs, M. F. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01413-x · Cited by 214 · see citing works
Role of lung and gut microbiota on lung cancer pathogenesis
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“Gut microbiome plays a crucial role in several diseases (Jobin 2012) especially in cancer.”
Remón, J., Passiglia, F., Ahn, M., Barlési, F., Forde, P. M., Garon, E. B., Gettinger, S. N., Goldberg, S. B., Herbst, R. S., Horn, L., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.03.006 · Cited by 168 · see citing works
“In a real-world study, Gopalakrishnan et al.(246) surveyed gut and oral”
BackgroundInfluentialSelf-citationAkkermansia muciniphila and Faecalibacterium prausnitzii in Immune-Related Diseases
Effendi, R. M. R. A., Anshory, M., Kalim, H., Dwiyana, R. F., Suwarsa, O., Pardo, L. M., Nijsten, T. E. C., & Thio, H. B. (2022) · Microorganisms · doi:10.3390/microorganisms10122382 · Cited by 190 · see citing works
Critical role of the gut microbiota in immune responses and cancer immunotherapy
Li, Z., Xiong, W., Zhu, L. W., Wang, J., Zeng, Z., Kołat, D., Li, X., Zhou, D., Xu, X., & Zhao, L.-Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01541-w · Cited by 188 · see citing works
“…responses of cancer patients ranging from those with melanoma to those with non-small cell lung carcinoma (NSCLC) have detected a greater frequency of memory CD8 + T cells and NK cells in the periphery of R enriched with Alis-tipes putredinis Bifidobacterium longum , and Prevotella copri [197].”
BackgroundThe curious case of Prevotella copri
Abdelsalam, N. A., Hegazy, S. M., & Aziz, R. K. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2249152 · Cited by 163 · see citing works
“copri, which synergizes with nivolumab’s action.(109) Glucagon-like peptide-1 receptor agonist (GLP1 RA) is an antidiabetic drug that induces variable responses in individuals.”
BackgroundVernocchi, P., Gili, T., Conte, F., CHIERICO, F. D., Conta, G., Miccheli, A., Botticelli, A., Paci, P., Caldarelli, G., Nuti, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228730 · Cited by 150 · see citing works
A gut microbial signature for combination immune checkpoint blockade across cancer types
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“As a (NSCLC) 4 , mesothelioma 5 and hepatocellular carcinoma 6 .”
InfluentialModulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy
Kang, X., Lau, H. C.-H., & Yu, J. Q. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101478 · Cited by 167 · see citing works
“55 A recent study in prostate cancer revealed that the fecal abundance of Streptococcus , particularly the oral bacterium Streptococcus salivarius , was significantly higher in pem-brolizumab responders.”
BackgroundLongitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma
Björk, J. R., Bolte, L. A., Maltez Thomas, A., Lee, K. A., Rossi, N., Wind, T. T., Smit, L. M., Armanini, F., Asnicar, F., Blanco-Miguez, A., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02803-3 · Cited by 156 · see citing works
Gut microbiota shapes cancer immunotherapy responses
Lei, W., Zhou, K., Lei, Y., Li, Q., & Zhu, H. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00786-8 · Cited by 166 · see citing works
“Prospectivestudieshavesince demonstrated signi fi cant correlations between microbiome composition and ICI outcomes in melanoma, NSCLC, and hepatocellular carcinoma (HCC) 46 – 49 .”
Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC
Niu, M., Yi, M., Li, N., Luo, S., & Wu, K. (2021) · Experimental Hematology and Oncology · doi:10.1186/s40164-021-00211-8 · Cited by 125 · see citing works
Microbiome dysbiosis in lung cancer: from composition to therapy
Liu, N., Ma, Q., Ge, Y., Yi, C., Wei, L., Tan, J.-C., Chu, Q., Li, J., Zhang, P., & Wang, H. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-00138-z · Cited by 145 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy
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“Such an imbalance of Firmicobacteria and Bacteroidetes increased the risk of lung cancer (1, 16, 24), and the diversity of gut microbiota in patients with lung cancer was positively correlated with the efficacy of immunotherapy (25, 26).”
BackgroundRole of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target
Zhang, M., Liu, J., & Xia, Q. (2023) · Experimental Hematology and Oncology · doi:10.1186/s40164-023-00442-x · Cited by 149 · see citing works
“Moreover, the high diversity of gut microbiome in responders remains stable during the immunotherapeutic process, which is different from the specific bacteria strains [41, 48, 55].”
BackgroundResultInfluentialExploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy
Qiu, Q., Lin, Y., Ma, Y., Li, X., Liang, J. B., Chen, Z., Liu, K., Huang, Y., Luo, H., Huang, R., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.612202 · Cited by 137 · see citing works
Sims, T. T., El Alam, M. B., Karpinets, T. V., Dorta-Estremera, S., Hegde, V. L., Nookala, S., Yoshida-Court, K., Wu, X., Biegert, G. W. G., Delgado Medrano, A. Y., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01741-x · Cited by 135 · see citing works
“The diversity of the gut microbiome is defined as the number and relative abundance distribution of these distinct types of microorganisms colonizing within the gut 7 .”
BackgroundThe gut–airway microbiome axis in health and respiratory diseases
Özçam, M., & Lynch, S. V. (2024) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01048-8 · Cited by 154 · see citing works
“Recently, patients with higher faecal microbiome diversity were found to experience prolonged progression-free survival — a length of time during and after a cancer treatment during which the disease does not worsen — compared with those who evidenced lower diversity 147 .”
Xu, L., Zhang, Y., Li, X., Li, C., Hu, H., Hu, J., Liu, M., Yang, Q. Z., Gu, P., Li, J., et al. (2025) · iMeta · doi:10.1002/imt2.270 · Cited by 138 · see citing works
Self-citationNeuro-immune crosstalk in cancer: mechanisms and therapeutic implications
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Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy
Shui, L., Yang, X., Li, J., Yi, C., Sun, Q., & Zhu, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02989 · Cited by 115 · see citing works
“(58) developed a clinical analysis to explore the relationship between gut microbiome and therapeutic outcomes in Chinese patients with advanced non-small-cell lung carcinoma who were being treated with PD-1 blockade therapies.”
BackgroundGut microbiota-mediated immunomodulation in tumor
Liu, X., Chen, Y., Zhang, S., & Dong, L. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01983-x · Cited by 112 · see citing works
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The gut microbiota in cancer immunity and immunotherapy
Xie, M., Li, X., Lau, H. C.-H., & Yu, J. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01326-2 · Cited by 125 · see citing works
“The human gastrointestinal tract harbors over 1000 microbial species from various kingdoms, including bacteria, prokaryotes, viruses, protists, and fungi [114].”
Chai, Y., Luo, J., & Bao, Y. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112155 · Cited by 102 · see citing works
The association between gut butyrate‐producing bacteria and non‐small‐cell lung cancer
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Diet, Microbiome, and Cancer Immunotherapy—A Comprehensive Review
Szczyrek, M., Bitkowska, P., Chunowski, P., Czuchryta, P., Krawczyk, P. A., & Milanowski, J. (2021) · Nutrients · doi:10.3390/nu13072217 · Cited by 102 · see citing works
“In patients with a poor response, enrichment of Ruminococcus unclassified was spotted in their gut [76].”
BackgroundInfluentialAghamajidi, A., & Vareki, S. M. (2022) · Cancers · doi:10.3390/cancers14153563 · Cited by 102 · see citing works
“A cohort study of 338 patients with NSCLC has demonstrated that intestinal Akkermansia muciniphila is significantly accompanied by clinical benefits with increased response rates and OS following PD-1 blockade [122].”
BackgroundMethodInfluentialKatayama, Y., Yamada, T., Shimamoto, T., Iwasaku, M., Kaneko, Y., Uchino, J., & Takayama, K. (2019) · Translational Lung Cancer Research · doi:10.21037/tlcr.2019.10.23 · Cited by 83 · see citing works
“23 effects of an anti-PD-1 antibody and the composition of the gut microbiome in malignant melanoma and NSCLC (8-11).”
BackgroundYin, J., Wu, Y., Yang, X., Gan, L., & Xue, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.830631 · Cited by 95 · see citing works
Tumor Immunology and Immunotherapy of Non-Small-Cell Lung CancerPreprint
Cascone, T., Fradette, J. J., Pradhan, M., & Gibbons, D. L. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a037895 · Cited by 85 · see citing works
Song, P., Yang, D., Wang, H., Cui, X., Si, X., Zhang, X., & Zhang, L. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13442 · Cited by 84 · see citing works
Zhang, C., Wang, J., Sun, Z., Cao, Y., Mu, Z., & Ji, X. (2021) · Cancer Science · doi:10.1111/cas.14979 · Cited by 79 · see citing works
Intratumor microbiome in cancer progression: current developments, challenges and future trends
Liu, J., & Zhang, Y. (2022) · Biomarker Research · doi:10.1186/s40364-022-00381-5 · Cited by 84 · see citing works
“The results of mouse models [21, 142] and a clinical trial (NCT03353402) have been promising [23, 30, 31, 136].”
BackgroundYang, Y. A., Yang, J., Shen, L., Chen, J., Xia, L., Ni, B., Ge, L., Wang, Y., & Lü, S. (2021) · PubMed Central · Cited by 76 · see citing works
Self-citationGut Microbiota: the Emerging Link to Lung Homeostasis and Disease
Zhou, A., Lei, Y., Tang, L., Hu, S., Yang, M., Wu, L., Yang, S., & Tang, B. (2020) · Journal of Bacteriology · doi:10.1128/jb.00454-20 · Cited by 78 · see citing works
“An increase in memory T and NK cells was observed in the peripheral blood samples of NSCLC patients with high gut microbiota diversity, which may be attributed to the differentiation of Th1 lymphocytes and M1 macrophages, upregulation of PD-1 expression on lymphocytes, and activation of helper/cytotoxic T cells (91).”
BackgroundThe potential role of the microbiota in prostate cancer pathogenesis and treatment
Pernigoni, N., Guo, C. W., Gallagher, L., Yuan, W., Colucci, M., Troiani, M., Liu, L., Maraccani, L., Guccini, I., Migliorini, D., et al. (2023) · Nature Reviews Urology · doi:10.1038/s41585-023-00795-2 · Cited by 68 · see citing works
Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment
Yang, X., Guo, Y., Chen, C., Shao, B., Zhao, L., Zhou, Q., Liu, J., Wang, G., Yuan, W., & Sun, Z. (2021) · Immunology · doi:10.1111/imm.13397 · Cited by 78 · see citing works
Tsikala-Vafea, M., Belani, N., Vieira, K., Khan, H., & Farmakiotis, D. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.03.063 · Cited by 76 · see citing works
Chau, J., Yadav, M., Liu, B., Furqan, M., Dai, Q., Shahi, S. K., Gupta, A. A., Mercer, K. N., Eastman, E., Hejleh, T. A., et al. (2021) · BMC Cancer · doi:10.1186/s12885-021-08530-z · Cited by 75 · see citing works
“This correlation appears to have an amplifying effect on treatment efficacy: in a 2019 study, survival also seemed to increase with increasing α-diversity [37].”
BackgroundThe gut microbiome and efficacy of cancer immunotherapy
Roviello, G., Iannone, L. F., Bersanelli, M., Mini, E., & Catalano, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107973 · Cited by 75 · see citing works
Microbiota-driven antitumour immunity mediated by dendritic cell migration
Lin, Y.-T., Fukuoka, S., Koyama, S., Motooka, D., Tourlousse, D. M., Shigeno, Y., Matsumoto, Y., Yamano, H., Murotomi, K., Tamaki, H., et al. (2025) · Nature · doi:10.1038/s41586-025-09249-8 · Cited by 81 · see citing works
“Our findings, together with previous reports 2,50–52 , suggest that gut microbiota diversity can serve as a pan-ethnic predictive biomarker for response to PD-1 blockade therapy across different cancer types.”
Lu, H., Gao, N. L., Wei, C., Wang, J., Tong, F., Li, H., Zhang, R., Ma, H., Yang, N., Zhang, Y., et al. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.00802-21 · Cited by 74 · see citing works
Self-citationLu, L., Dong, J., Liu, Y., Qian, Y., Zhang, G., Zhou, W., Zhao, A., Ji, G., & Xu, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.964793 · Cited by 73 · see citing works
“Experiments in which colitis was induced by DSS administration demonstrated that oroxylin A, a natural flavonoid, reduces susceptibility to colitis and prevents carcinogenesis in colon (Jung et al., 2012).”
Background<i>Faecalibacterium prausnitzii</i> 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 · see citing works
“2,6,7 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.”
Crespin, A., Bescop, C. L., de Gunzburg, J., Vitry, F., Zalcman, G., Cervesi, J., & Bandinelli, P.-A. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1075593 · Cited by 73 · see citing works
“A high gut microbiome diversity at baseline was for example significantly associated with favorable clinical outcomes in several studies on NSCLC and melanoma patients (49, 56, 142).”
BackgroundThe gut microbiome and cancer response to immune checkpoint inhibitors
Gazzaniga, F. S., & Kasper, D. L. (2025) · Journal of Clinical Investigation · doi:10.1172/jci184321 · Cited by 80 · see citing works
Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy
Yi, M., Jiao, D., Qin, S., Chu, Q., Li, A., & Wu, K. (2019) · Integrative Cancer Therapies · doi:10.1177/1534735419876351 · Cited by 69 · see citing works
Liu, X., Wang, L., Jing, N., Jiang, G., & Liu, Z. (2020) · Microorganisms · doi:10.3390/microorganisms8020175 · Cited by 67 · see citing works
“Higher species diversity is correlated with higher response rates to ICIs [30,31], hence we analyzed the alpha diversity.”
BackgroundPeiffer, L. B., White, J. R., Jones, C. B., Slottke, R., Ernst, S. E., Moran, A. E., Graff, J. N., & Sfanos, K. S. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100822 · Cited by 62 · see citing works
Zhao, Z., Fei, K., Bai, H., Wang, Z., Duan, J., & Wang, J. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13711 · Cited by 68 · see citing works
Zhu, R., Lang, T., Yan, W., Zhu, X. G., Huang, X. Y., Yin, Q., & Li, Y. (2021) · Advanced Science · doi:10.1002/advs.202003542 · Cited by 65 · see citing works
Segers, A., & de Vos, W. M. (2023) · Microbiome Research Reports · doi:10.20517/mrr.2023.05 · Cited by 67 · see citing works
Oh, B., Boyle, F. M., Pavlakis, N., Clarke, S. J., Eade, T., Hruby, G., Lamoury, G., Carroll, S. L., Morgia, M., Kneebone, A. B., et al. (2021) · Cancers · doi:10.3390/cancers13194824 · Cited by 66 · see citing works
“, [25] 2019 China Advanced NSCLC (n = 37) M: 78% Anti-PD-1 Chemotherapy before ICI ATB usage (n = 11) Fecal multiple times V3–V4 region 16S rRNA gene sequencing PFS PFS was significantly prolonged in patients who harbored high-diversity microbiota when compared to the low-diversity group.”
BackgroundDóra, D., Ligeti, B., Kovács, T., Revisnyei, P., Gálffy, G., Dulka, E., Krizsán, D., Kalcsevszki, R., Megyesfalvi, Z., Döme, B., et al. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2204746 · Cited by 61 · see citing works
“It is important to highlight that previous NSCLC studies interpreting alpha-diversity and taxonomic profiles according to ICI-response 16,17 used 16S rRNA sequencing works with distinct reference datasets and limited taxonomical scope compared to shotgun metagenomics.”
InfluentialHuang, C.-L., Li, M., Liu, B., Zhu, H., Dai, Q., Fan, X., Mehta, K. D., Huang, C. H., Neupane, P. C., Wang, F., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.642110 · Cited by 56 · see citing works
“Although there are studies correlating phylum Bacteroidetes with poor response from ICIs (12, 17), we also observed several other studies were suggestive of a positive impact (6, 13, 18).”
ResultGut Microbiota in Lung Cancer: Where Do We Stand?
Georgiou, K. E., Marinov, B. I., Farooqı, A. A., & Gazouli, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910429 · Cited by 60 · see citing works
“Moreover, extended progression-free survival (PFS) has been shown in patients with high microbiome diversity as compared to those presenting low diversity [113].”
BackgroundPan, Y., Fu, Y., Zeng, Y., Liu, X., Peng, Y., Hu, C., Deng, C., Qiu, Z., Zou, J. P., Liu, Y., et al. (2022) · Biomarker Research · doi:10.1186/s40364-022-00355-7 · Cited by 59 · see citing works
“The diversity of intestinal flora is closely related to the effectiveness of ICIs in patients with advanced NSCLC, and the higher the diversity of intestinal flora, the better the efficacy [101, 102].”
BackgroundGut Microbiota and Lung Injury
Tan, J.-Y., Tang, Y., & Huang, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-2385-4_5 · Cited by 61 · see citing works
The role of microbiome in pancreatic cancer
Li, J., Zhu, M., Kashyap, P., Chia, N., Tran, N. H., McWilliams, R. R., Bekaii‐Saab, T., & Ma, W. W. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09982-2 · Cited by 58 · see citing works
The role of the gut microbiota in gastric cancer: the immunoregulation and immunotherapy
Wang, M., Yang, G., Tian, Y., Zhang, Q., Liu, Z., & Xin, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1183331 · Cited by 59 · see citing works
Microbiome dysbiosis and epigenetic modulations in lung cancer: From pathogenesis to therapy
Khan, F. H., Bhat, B. A., Sheikh, B. A., Tariq, L., Padmanabhan, R., Verma, J. P., Shukla, A. C., Dowlati, A., & Abbas, A. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.07.005 · Cited by 59 · see citing works
Huang, J., Jiang, Z., Wang, Y., Fan, X., Cai, J., Yao, X., Liu, L., Huang, J., He, J., Xie, C., et al. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.06.004 · Cited by 56 · see citing works
Self-citationTumour neoantigen mimicry by microbial species in cancer immunotherapy
Boesch, M., Baty, F., Rothschild, S. I., Tamm, M., Joerger, M., Früh, M., & Brutsche, M. H. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01365-2 · Cited by 52 · see citing works
“First, co-treatment with antibiotics (which reduces potential mimicry) and organism-wide germ elimination (which precludes mimicry) are well-known to curtail the efficacy of checkpoint-based immunotherapy73–75,79,150—with the limitation that clinical data are derived almost exclusively retrospectively, as prospective…”
ResultCao, C., Yue, S., Lü, A., & Liang, C. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107321 · Cited by 59 · see citing works
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 59 · see citing works
“59 82–85 Similarly, Pederzoli et al. reported that patients with muscle-invasive urothelial carcinoma who were unresponsive to anti-PD-1 had a higher prevalence of R. bromii (Figure 2).”
BackgroundThe Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions
Kiousi, D. E., Kouroutzidou, A. Z., Neanidis, K., Karavanis, E., Matthaios, D., Pappa, A., & Galanis, Α. (2023) · Cancers · doi:10.3390/cancers15072101 · Cited by 58 · see citing works
“Single group, open label Phase I NCT04521075 Recruiting MM (IV) Unresectable Melanoma (III) NSCLC (IV) 42 PD-1 blockade FMT (oral capsules) Donors: Patients with DR, CR FMT-related AE, ORR, PFS, OS, DoR, irAEs, immune activation markers Single group, open label Phase I and II NCT04577729 Recruiting Melanoma(III–IV) 60…”
BackgroundInfluentialGut microbiota: impacts on gastrointestinal cancer immunotherapy
Lau, H. C.-H., Sung, J. J. �., & Yu, J. Q. (2021) · Gut Microbes · doi:10.1080/19490976.2020.1869504 · Cited by 56 · see citing works
“Some of these species include B. longum, Collinsella aerofaciens, and Enterococcus faecium in metastatic melanoma ;26,29 and B. longum, Akkermansia muciniphila, and Prevotella corpri in NSCLC and RCC.28,30 To establish a cause–effect relationship between commensals and blockade efficacy, feces from responding patients…”
The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer
Halley, A., Leonetti, A., Gregori, A., Tiseo, M., Deng, D., Giovannetti, E., & Peters, G. J. (2020) · Anticancer Research · doi:10.21873/anticanres.14484 · Cited by 52 · see citing works
Yang, M., Guo, J., Li, J., Wang, S., Sun, Y., Liu, Y., & Peng, Y. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03139-x · Cited by 64 · see citing works
Metabolic regulation of T cells in the tumor microenvironment by nutrient availability and diet
Zhao, S., Peralta, R. M., Avina-Ochoa, N., Delgoffe, G. M., & Kaech, S. M. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101485 · Cited by 57 · see citing works
Lung and Gut Microbiota as Potential Hidden Driver of Immunotherapy Efficacy in Lung Cancer
Carbone, C., Piro, G., Noia, V. D., D’Argento, E., Vita, E., Ferrara, M. G., Pilotto, S., Milella, M., Cammarota, G., Gasbarrini, A., et al. (2019) · Mediators of Inflammation · doi:10.1155/2019/7652014 · Cited by 54 · see citing works
Guan, X., Ma, F., Sun, X., Li, C., Li, L., Liang, F., Li, S., Yi, Z., Liu, B., & Xu, B. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00902 · Cited by 52 · see citing works
“In addition, in a Chinese cohort of advanced non-small cell lung cancer patients receiving the treatment of anti-programmed death 1 (PD-1) blockade, patients with better clinical responses exhibited higher gut microbiome diversity (32).”
BackgroundZhu, C., Zhang, C., Wang, S., Xun, Z., Zhang, D., Lan, Z., Zhang, L., Chao, J., Liang, Y., Pu, Z., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008686 · Cited by 60 · see citing works
Zhao, H., Li, D., Liu, J., Zhou, X., Han, J., Wang, L., Fan, Z., Li, F., Zuo, J., & Wang, Y. (2022) · Cancer Medicine · doi:10.1002/cam4.5312 · Cited by 47 · see citing works
Self-citationMicrobes in lung cancer initiation, treatment, and outcome: Boon or bane?
Guo, H., Zhao, L., Zhu, J., Chen, P., Wang, H., Jiang, M., Liu, X., Sun, H., Zhao, W., Zheng, Z., et al. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.025 · Cited by 46 · see citing works
Self-citationProgresses in biomarkers for cancer immunotherapy
Lin, X., Zong, C., Zhang, Z., Fang, W., & Xu, P. (2023) · MedComm · doi:10.1002/mco2.387 · Cited by 48 · see citing works
Gut microbiome and response to checkpoint inhibitors in non-small cell lung cancer—A review
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Shaikh, F. Y., White, J. R., Gills, J. J., Hakozaki, T., Richard, C., Routy, B., Okuma, Y., Usyk, M., Pandey, A., Weber, J. S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4834 · Cited by 44 · see citing works
Ni, B., Kong, X., Yan, Y., Fu, B., Zhou, F., & Xu, S. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1091825 · Cited by 45 · see citing works
Pradhan, M., Chocry, M., Gibbons, D. L., Sepesi, B., & Cascone, T. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-573 · Cited by 44 · see citing works
- Authors
- Jin, Y., Dong, H., Xia, L., Yang, Y., Zhu, Y., Shen, Y., Zheng, H., Yao, C., Wang, Y., & Lu, S.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Chinese National Human Genome Center at Shanghai (CN)
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 14
- Issue
- 8
- Pages
- 1378-1389
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W2942123458
- Cited by
- 573
- References
- 56
- Citations by year
- 2026: 71 · 2025: 100 · 2024: 97 · 2023: 91 · 2022: 71 · 2021: 90 · 2020: 43 · 2019: 10
- FWCI
- 22.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- gut microbiota, microbiome diversity, non-small cell lung cancer, anti-PD-1 therapy, nivolumab, immune checkpoint inhibitors, treatment response prediction, progression-free survival, memory CD8+ T cells, natural killer cells, Alistipes putredinis, Bifidobacterium longum, Prevotella copri, Ruminococcus, Chinese patients
- MeSH terms
- Gastrointestinal Microbiome, Antineoplastic Agents, Immunological, Nivolumab, Carcinoma, Non-Small-Cell Lung, Clinical Trials as Topic, Feces, Female, Humans, Lung Neoplasms, Male, Middle Aged, Disease Progression, Asian People, Programmed Cell Death 1 Receptor
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