Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2025-1-29

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

39481388

DOI Digital object identifier for electronic documents.

10.1016/j.chom.2024.10.006

URI

Authors

Macandog ADG, Catozzi C, Capone M, Nabinejad A, Nanaware PP, Liu S, Vinjamuri S, Stunnenberg JA, Galiè S, Jodice MG, Montani F, Armanini F, Cassano E, Madonna G, Mallardo D, Mazzi B, Pece S, Tagliamonte M, Vanella V, Barberis M, Ferrucci PF, Blank CU, Bouvier M, Andrews MC, Xu X, Santambrogio L, Segata N, Buonaguro L, Cocorocchio E, Ascierto PA, Manzo T, Nezi L

Journal

Cell host & microbe

Year

2024

Keywords:

antigen mimicry, gut microbiome, immunotherapy, longitudinal, melanoma

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach-reactive CD8+ T cells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides.

Experiment 1

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Curated date: 2024/11/19

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Subjects

Location of subjects

Italy

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

Melanoma malignant melanoma,melanoma,melanoma (disease),melanoma, malignant,Naevocarcinoma,Melanoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies

non-complete responders (nCR)

Group 1 name Corresponds to the case (exposed) group for case-control studies

complete responders (CR)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

This group represents the Complete Responders (CR) to anti-PD-1 therapy in melanoma patients for 2-6 months (early therapy) .

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

7

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

25

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

30 days

Lab analysis

Sequencing type

16S

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

V3-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).

log transformation

Statistical test

MaAsLin2

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 Svetlana up on 2025-1-29

Curated date: 2024/11/19

Curator: Joiejoie

Revision editor(s): Joiejoie, Aleru Divine, WikiWorks

Source: Figure S2D

Description: Differential abundance of CR (blue) and ncR (red) stable taxa on log-transformed relative abundance, based on Maaslin2 linear model (LM) coefficient.

Abundance in Group 1: increased abundance in

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Bacteroides nordii
Bifidobacterium pseudolongum
Bifidobacterium pullorum
Candidatus Heteroscillospira lomanii
Candidatus Metalachnospira gallinarum
Candidatus Metaruminococcus gallistercoris
Candidatus Roslinia caecavium
Clostridia unclassified SGB14016Clostridia unclassified SGB14016
Candidatus Gallimonas caecicola
Veillonellaceae SGB5809 groupVeillonellaceae SGB5809 group

Revision editor(s): Joiejoie, Aleru Divine, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2025-1-29

Curated date: 2025/01/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure S2D

Description: Differential abundance of CR (blue) and ncR (red) stable taxa on log-transformed relative abundance, based on Maaslin2 linear model (LM) coefficient.

Abundance in Group 1: decreased abundance in

NCBI	Quality Control	Links
Alistipes sp. An66

Revision editor(s): Aleru Divine, WikiWorks

Experiment 2

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Curated date: 2024/11/22

Curator: Joiejoie

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Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

This group represents the Complete Responders (CR) to anti-PD-1 therapy in melanoma patients for 7-13 months (late therapy).

Lab analysis

Sequencing type

WMS

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

Not specified

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-1-29

Curated date: 2024/11/27

Curator: Joiejoie

Revision editor(s): Joiejoie, Aleru Divine, WikiWorks

Source: Figure S2D

Description: Differential abundance of CR (blue) and ncR (red) stable taxa on log-transformed relative abundance, based on Maaslin2 linear model (LM) coefficient.

Abundance in Group 1: increased abundance in complete responders (CR)

NCBI	Quality Control	Links
Clostridia unclassified SGB14951Clostridia unclassified SGB14951
Candidatus Metaruminococcus gallistercoris
Clostridia unclassified SGB14016Clostridia unclassified SGB14016
Candidatus Metalachnospira gallinarum
Veillonellaceae SGB5809 groupVeillonellaceae SGB5809 group
Bacteroides nordii
Evtepia gabavorous
Clostridium SGB6179Clostridium SGB6179
Bifidobacterium pullorum

Revision editor(s): Joiejoie, Aleru Divine, WikiWorks

Signature 2

EditHistoryDelete

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Your review change was submitted

Reviewed Marked as Reviewed by Svetlana up on 2025-1-29

Curated date: 2025/01/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure S2D

Description: Differential abundance of CR (blue) and ncR (red) stable taxa on log-transformed relative abundance, based on Maaslin2 linear model (LM) coefficient.

Abundance in Group 1: decreased abundance in complete responders (CR)

NCBI	Quality Control	Links
Alistipes sp. An66
Bacteroides sp. Marseille-P3684

Revision editor(s): Aleru Divine, WikiWorks