Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors

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    • Batch effect issues suspected
    • Uncontrolled confounding suspected
    • Results are suspect (various reasons)
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Needs review
study design
time series / longitudinal observational
Citation
PMID PubMed identifier for scientific articles.
29097494
DOI Digital object identifier for electronic documents.
10.1126/science.aan3706
URI
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


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Curated date: 2021/01/10

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Subjects

Location of subjects
France
Host species Species from which microbiome was sampled. Contact us to have more species added.
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
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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

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Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

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 Quality ControlLinks
Akkermansia muciniphila   
Eubacterium sp.   
Lachnospiraceae   
Erysipelotrichaceae   
Intestinimonas   
Alistipes finegoldii   
Bacteroides sp.   
Cloacibacillus porcorum   
Enterococcus faecium   
Prevotella   

Revision editor(s): WikiWorks

Signature 2

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Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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

NCBI Quality ControlLinks
Bacillota bacterium   
Bacteroides clarus   
Bacteroides nordii   
Blautia   
Clostridium sp.   
Enterocloster bolteae   
Eubacteriales   
Parabacteroides distasonis   
Prevotella   
Pseudomonadota   
Clostridiales bacterium   

Revision editor(s): Atrayees, WikiWorks

Experiment 2


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Differences from previous experiment shown

Subjects

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
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified
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

Statistical Analysis

Signature 1

EditHistoryDelete
Mark reviewed
Your review change was submitted
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Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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

NCBI Quality ControlLinks
Akkermansia muciniphila   
Alistipes   
Bacillota   
Bacteroides nordii   
Bacteroides xylanisolvens   
Blautia   
Clostridium sp.   
Eubacteriales   
Eubacterium sp.   
Flavonifractor plautii   
Intestinimonas   
Lachnospiraceae   
Ruminococcus   
Ruminococcus sp.   
Bacteroides caccae   
Bacillota bacterium   

Revision editor(s): Atrayees, WikiWorks

Signature 2

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 Quality ControlLinks
Anaerotruncus colihominis   
Erysipelotrichaceae   
Eubacteriales   
Lachnospiraceae   
Parabacteroides distasonis   
Bacillota bacterium   

Revision editor(s): Atrayees, WikiWorks

Experiment 3


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Mark reviewed
Your review change was submittedDuplicate this ExperimentAdd a new Signature
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Curated date: 2021/01/10

Curator: WikiWorks

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Differences from previous experiment shown

Subjects

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
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Mass spectrometry

Statistical Analysis

Signature 1

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Mark reviewed
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Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

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 Quality ControlLinks
Staphylococcus haemolyticus   
Corynebacterium aurimucosum   

Revision editor(s): WikiWorks

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