Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L
Journal
Science (New York, N.Y.)
Year
2018
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
Experiment 1
Subjects
- Location of subjects
- France
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- non-small cell lung carcinoma , renal cell carcinoma non-small cell cancer of lung,non-small cell cancer of the lung,non-small cell carcinoma of lung,non-small cell carcinoma of the lung,non-small cell lung cancer,non-small cell lung carcinoma,non-small cell lung carcinoma (disease),NSCLC,NSCLC - non-small cell lung cancer,hypernephroma,kidney adenocarcinoma,RCC,renal cell adenocarcinoma,renal cell carcinoma,renal cell carcinoma (disease)
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- non-small cell lung carcinoma or renal carcinoma patients (all samples regardless of ampicillin, colistin, and streptomycin (ATB) anitbiotic treatment) that have been treated with PD-1 blockage with partial response or stable disease
- Group 0 sample size Number of subjects in the control (unexposed) group
- 36
- Group 1 sample size Number of subjects in the case (exposed) group
- 42
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Ion Torrent
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Needs review
Source: Figure 2b, Supplemental Figure S4
Description: Comparsion of partial response/ stable disease and progressive disease in fecal samples of all patients with non-small cell lung cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) reponse at 3 months of PD-1 monoclonal antibodies (mAB) treatment
Abundance in Group 1: increased abundance in Responders
| NCBI | Links |
|---|---|
| Akkermansia muciniphila | |
| Eubacterium sp. | |
| Lachnospiraceae | |
| Erysipelotrichaceae | |
| Intestinimonas | |
| Alistipes finegoldii | |
| Bacteroides sp. | |
| Cloacibacillus porcorum | |
| Enterococcus faecium | |
| Prevotella |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 2b, Supplemental Figure S4
Description: Comparsion of partial response/ stable disease and progressive disease in fecal samples of all patients with non-small cell lung cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) reponse at 3 months of PD-1 monoclonal antibodies (mAB) treatment
Abundance in Group 1: decreased abundance in Responders
Experiment 2
Subjects
- Location of subjects
- France
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- non-small cell lung carcinoma , renal cell carcinoma non-small cell cancer of lung,non-small cell cancer of the lung,non-small cell carcinoma of lung,non-small cell carcinoma of the lung,non-small cell lung cancer,non-small cell lung carcinoma,non-small cell lung carcinoma (disease),NSCLC,NSCLC - non-small cell lung cancer,hypernephroma,kidney adenocarcinoma,RCC,renal cell adenocarcinoma,renal cell carcinoma,renal cell carcinoma (disease)
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Progressive- Free- Survival more less than 30 days
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Progressive -Free- Survival more than 30 days
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- non-small cell lung carcinoma or renal carcinoma patients (excluding ampicillin, colistin, and streptomycin (ATB) anitbiotic treatment) that have been treated with PD-1 blockage with partial response or stable disease that are Progressive- Free- Survival greater than 3 months
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- ampicillin, colistin, and streptomycin
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Ion Torrent
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Needs review
Source: Figure 2c, Supplemental Figure S5b
Description: Comparsion of patients with partial progressive survival free more than 3 months and less than 3 in fecal samples of patients (excluding those treated with antibiotics) with non-small cell lung cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) reponse at 3 months of PD-1 monoclonal antibodies (mAB) treatment
Abundance in Group 1: increased abundance in Progressive -Free- Survival more than 30 days
Signature 2
Needs review
Source: Figure 2c, Supplemental Figure S5b
Description: Comparsion of patients with partial progressive survival free more than 3 months and less than 3 in fecal samples of patients (excluding those treated with antibiotics) with non-small cell lung cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) reponse at 3 months of PD-1 monoclonal antibodies (mAB) treatment
Abundance in Group 1: decreased abundance in Progressive -Free- Survival more than 30 days
| NCBI | Links |
|---|---|
| Anaerotruncus colihominis | |
| Erysipelotrichaceae | |
| Eubacteriales | |
| Lachnospiraceae | |
| Parabacteroides distasonis | |
| Bacillota bacterium |
Experiment 3
Subjects
- Location of subjects
- France
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- non-small cell lung carcinoma , renal cell carcinoma non-small cell cancer of lung,non-small cell cancer of the lung,non-small cell carcinoma of lung,non-small cell carcinoma of the lung,non-small cell lung cancer,non-small cell lung carcinoma,non-small cell lung carcinoma (disease),NSCLC,NSCLC - non-small cell lung cancer,hypernephroma,kidney adenocarcinoma,RCC,renal cell adenocarcinoma,renal cell carcinoma,renal cell carcinoma (disease)
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- non-small cell lung carcinoma or renal carcinoma patients (all samples regardless of ampicillin, colistin, and streptomycin (ATB) anitbiotic treatment) that have been treated with PD-1 blockage with partial response or stable disease
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- Group 1 sample size Number of subjects in the case (exposed) group
- 16
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Mass spectrometry
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Needs review
Source: Figure 2g
Description: Culturomics-based analyses of fecal samples in 16 Responders and 16 Non-Responders Non-Small Cell Lung Carcinoma patients (defined as the best clinical outcome) before PD-1 blockage immunotherapy, each commensal colony having been identified by mass spectrometry
Abundance in Group 1: decreased abundance in Responders
| NCBI | Links |
|---|---|
| Staphylococcus haemolyticus | |
| Corynebacterium aurimucosum |
Revision editor(s): WikiWorks
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