Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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
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
- Response to immune checkpoint inhibitor response to ICI,Response to immune checkpoint inhibitor,response to immune checkpoint inhibitor
- 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
- The complete responders (CR) are defined as patients who exhibit a complete response to treatment, characterized by a significant reduction or disappearance of tumors. This is determined through clinical evaluations and imaging assessments during the treatment course. The study highlights that the ORR for the patient cohort was 56%, with CRs demonstrating stable gut microbiota features that correlate with their positive clinical outcomes during anti-PD-1 therapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 14
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- The study specifies that participants were excluded if they had used antibiotics within 30 days prior to the start of anti-PD-1 therapy. This exclusion criterion is important as antibiotics can significantly impact gut microbiota composition, which is a key focus of the study in relation to treatment response.
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).
- centered log-ratio
- 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)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.0
- Matched on Factors on which subjects have been matched on in a case-control study
- age
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, Confounders controlled for: "gender" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gender, Confounders controlled for: "clinical characteristics" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.clinical characteristics
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- increased
Signature 1
Source: Figure S2D
Description: This figure highlights the microbial taxa dynamics associated with treatment response, emphasizing the potential role of specific gut microbiota in influencing clinical outcomes during anti-PD-1 therapy.
Abundance in Group 1: increased abundance in complete responders (CR)
Revision editor(s): Joiejoie
Signature 2
Source: Figure S2D
Description: This figure highlights the microbial taxa dynamics associated with treatment response, emphasizing the potential role of specific gut microbiota in influencing clinical outcomes during anti-PD-1 therapy.
Abundance in Group 1: decreased abundance in complete responders (CR)
Revision editor(s): Joiejoie
Experiment 2
Differences from previous experiment shown
Subjects
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
Statistical Analysis
- Statistical test
- MaAsLin2
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 0
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- increased
Signature 1
Source: S1B
Description: Highlights the longitudinal profiling of gut microbiota changes associated with treatment response. It compares the stable taxa identified in complete responders (CR) and non-complete responders (nCR) at various time points throughout the therapy.
Abundance in Group 1: increased abundance in complete responders (CR)
| NCBI | Quality Control | Links |
|---|---|---|
Revision editor(s): Joiejoie
Signature 2
Source: Figure S1B
Description: Highlights the longitudinal profiling of gut microbiota changes associated with treatment response. It compares the stable taxa identified in complete responders (CR) and non-complete responders (nCR) at various time points throughout the therapy.
Abundance in Group 1: decreased abundance in complete responders (CR)
| NCBI | Quality Control | Links |
|---|---|---|
Revision editor(s): Joiejoie
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