The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients

Study information

Reviewed Marked as Reviewed by Fatima on 2022/08/24

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

29302014

DOI Digital object identifier for electronic documents.

10.1126/science.aao3290

URI

https://pubmed.ncbi.nlm.nih.gov/29302014/

Authors

Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF

Journal

Science (New York, N.Y.)

Year

2018

Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/08/24

Curated date: 2022/07/28

Curator: Sharmilac

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

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 0 sample size Number of subjects in the control (unexposed) group: 26

Group 1 sample size Number of subjects in the case (exposed) group: 16

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

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: T-Test

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)?: Yes

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/08/24

Curated date: 2022/07/28

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima

Source: Figure 1, text

Description: Relative abundance of differentially abundant taxa in responders versus nonresponders;

Abundance in Group 1: increased abundance in Responders

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Bifidobacteriaceae

Revision editor(s): Sharmilac, Fatima

Experiment 2

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Curated date: 2022/08/24

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Differences from previous experiment shown

Subjects

Lab analysis

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: RT-qPCR

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified

Statistical test: Mann-Whitney (Wilcoxon)

Signature 1

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Source: text, Figure 2

Description: Quantitative PCR score representing aggregate data for the relative abundances of 10 species

Abundance in Group 1: increased abundance in Responders

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Parabacteroides
Enterococcus faecium
Collinsella aerofaciens
Bifidobacterium adolescentis
Klebsiella pneumoniae
Veillonella parvula
Parabacteroides merdae
Lactobacillus sp.
Bifidobacterium longum

Revision editor(s): Fatima

Signature 2

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Source: text, Figure 2

Description: Quantitative PCR score representing aggregate data for the relative abundances of 10 species

Abundance in Group 1: decreased abundance in Responders

NCBI	Quality Control	Links
Blautia obeum CAG:39
Roseburia intestinalis

Revision editor(s): Fatima

Experiment 3

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Reviewed Marked as Reviewed by Fatima on 2022/08/24

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima, Sharmilac

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Non-responders, group B

Group 1 name Corresponds to the case (exposed) group for case-control studies: Responders, group A

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Mouse with 16.SIY melanoma tumor growth