Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients

Study information

Reviewed Marked as Reviewed by Fatima on 2022/09/5

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

29097493

DOI Digital object identifier for electronic documents.

10.1126/science.aan4236

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827966/

Authors

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA

Journal

Science (New York, N.Y.)

Year

2018

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Experiment 2

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Reviewed Marked as Reviewed by Fatima on 2022/09/5

Curated date: 2022/08/30

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima, Peace Sandy

Differences from previous experiment shown

Subjects

Location of subjects: United States of America

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,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Response to immunochemotherapy Response to immunochemotherapy,response to immunochemotherapy

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: Patients were classified as R if they achieved an objective response (complete or partial response or stable disease lasting at least 6 months)

Group 0 sample size Number of subjects in the control (unexposed) group: 35

Group 1 sample size Number of subjects in the case (exposed) group: 54

Lab analysis

Sequencing type: 16S

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: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: increased

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/09/5

Curated date: 2022/08/30

Curator: Sharmilac

Revision editor(s): Sharmilac

Source: Figure 2D

Description: (D) LDA scores computed for differentially-abundant taxa in the fecal microbiomes of R (blue) and NR (red). Length indicates effect size associated with a taxon. p=0.05 for the Kruskal-Wallis test; LDA score > 3.

Abundance in Group 1: increased abundance in Responders

NCBI	Quality Control	Links
Bacillota
Clostridia
Clostridiales bacterium
Oscillospiraceae
Faecalibacterium prausnitzii
Faecalibacterium
Ruminococcus bromii
Ruminococcus
Porphyromonas pasteri
Veillonellaceae
Ruminiclostridium hungatei
Phascolarctobacterium
Phascolarctobacterium faecium
Peptoniphilus
Micrococcaceae
Mollicutes
Rothia

Revision editor(s): Sharmilac

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/09/5

Curated date: 2022/08/30

Curator: Sharmilac

Revision editor(s): Sharmilac

Source: Figure 2D

Description: (D) LDA scores computed for differentially-abundant taxa in the fecal microbiomes of R (blue) and NR (red). Length indicates effect size associated with a taxon. p=0.05 for the Kruskal-Wallis test; LDA score > 3.

Abundance in Group 1: decreased abundance in Responders

NCBI	Quality Control	Links
Collinsella stercoris
Oleidesulfovibrio alaskensis
Bacteroides mediterraneensis
Prevotella histicola
Gardnerella vaginalis
Gardnerella
Bacteroidota
Bacteroidales
Bacteroidia

Revision editor(s): Sharmilac