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

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Reviewed Marked as Reviewed by Fatima on 2022/08/24
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

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

NCBI Quality ControlLinks
Bifidobacteriaceae

Revision editor(s): Sharmilac, Fatima

Experiment 2


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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima, Sharmilac, Victoria

Differences from previous experiment shown

Subjects

Lab analysis

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

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)


Signature 1

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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima

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

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

Revision editor(s): Fatima

Signature 2

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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima

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 ControlLinks
Blautia obeum CAG:39
Roseburia intestinalis

Revision editor(s): Fatima

Experiment 3


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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima, Sharmilac, Victoria

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
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
3

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified

Statistical Analysis

Signature 1

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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima

Source: Figure 3

Description: Relative abundance in mouse groups A and b of key species validated for quantitative PCR

Abundance in Group 1: increased abundance in Responders, group A

NCBI Quality ControlLinks
Collinsella aerofaciens
Bifidobacterium longum
Lactobacillus sp.
Klebsiella pneumoniae
Parabacteroides merdae

Revision editor(s): Fatima

Signature 2

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

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima

Source: Figure 3

Description: Relative abundance in mouse groups A an B of key species validated for quantitative PCR scoring.

Abundance in Group 1: decreased abundance in Responders, group A

NCBI Quality ControlLinks
Roseburia intestinalis

Revision editor(s): Fatima