Gut microbiome features associate with immune checkpoint inhibitor response in individuals with non-melanoma skin cancers: an exploratory study
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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
Zhao Y, Ferri JT, White JR, Schollenberger MD, Peloza K, Sears CL, Lipson EJ, Shaikh FY
Journal
Microbiology spectrum
Year
2025
Keywords:
Merkel cell carcinoma, basal cell carcinoma, cutaneous squamous cell carcinoma, immune checkpoint inhibitors, microbiome
Immune checkpoint inhibitor (ICI) therapy has yielded revolutionary outcomes among some individuals with skin cancer, but a large percentage of individuals do not benefit from these treatments. The gut microbiota is hypothesized to impact ICI therapy outcomes. However, data on ICI therapy, gut microbiota, and non-melanoma skin cancers are limited. To examine the association of gut microbiota structure and function with non-melanoma skin cancer ICI outcomes, we performed 16S rRNA V1-V2 gene amplicon sequencing of 68 fecal samples collected longitudinally from individuals with basal cell carcinoma (n = 5), Merkel cell carcinoma (n = 5), or cutaneous squamous cell carcinoma (CSCC, n = 11), followed by tumor-dependent differential analyses of bacterial composition and fecal sample analysis by untargeted metabolomics. Across all tumor types, we identified 10 differential bacterial genera between responders (R) or non-responders (NR) to ICI therapy. Among individuals with CSCC, we identified 10 genera and 20 species that differentiated between R and NR and yielded 8 pathways enriched in NR and 12 pathways enriched in R by predicted functional pathway analyses. Untargeted fecal metabolomics to examine putative gut microbiota metabolites associated with CSCC ICI R/NR identified nine KEGG pathways associated with ICI efficacy. In summary, this exploratory study suggests gut microbiota features that are associated with ICI efficacy in individuals with non-melanoma skin cancers and highlights the need for larger studies to validate the results.IMPORTANCEPrior studies examining associations between ICI efficacy and the gut microbiome have focused primarily on individuals with melanoma, for whom ICI therapy was first approved. Meanwhile, data regarding microbiome features associated with ICI responses in individuals with non-melanoma skin cancers (NMSCs) have remained limited. This initial fecal microbiota examination of individuals with NMSCs suggests that larger-scale studies to extend and validate our findings may yield predictive or prognostic biomarkers for individuals with NMSC receiving ICI with potential to provide insight to complementary, effective therapeutic interventions through microbiota modification.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
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 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-responders (NR)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (R)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of individual responders (R) to Immune checkpoint inhibitor (ICI) therapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V2
- 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)
- 0.1
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Fig. 1C
Description: Differential abundance analysis performed by linear discriminant analysis effect size using the first fecal sample of each individual collected within 180 days.
Abundance in Group 1: increased abundance in Responders (R)
| NCBI | Quality Control | Links |
|---|---|---|
| Acetomicrobium | ||
| Actinomyces | ||
| Anaerofustis | ||
| Barnesiella | ||
| Clostridium | ||
| Holdemania | ||
| Mahella | ||
| Adlercreutzia | ||
| Ruminococcus | ||
| Hydrogenoanaerobacterium |
Revision editor(s): Joiejoie
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Cutaneous squamous cell carcinoma Non-responders (CSCC NR)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cutaneous squamous cell carcinoma Responders (CSCC R)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group comprises individuals with Cutaneous squamous cell carcinoma who are responders to Immune checkpoint inhibitor (ICI) therapy.
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Fig. 2A
Description: Differential abundance analysis performed by linear discriminant analysis effect size (LEfSe) using the first fecal sample for each individual collected within 180 days in CSCC.
Abundance in Group 1: increased abundance in Cutaneous squamous cell carcinoma Responders (CSCC R)
Revision editor(s): Joiejoie
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Fig. 2A
Description: Differential abundance analysis performed by linear discriminant analysis effect size (LEfSe) using the first fecal sample for each individual collected within 180 days in CSCC.
Abundance in Group 1: decreased abundance in Cutaneous squamous cell carcinoma Responders (CSCC R)
| NCBI | Quality Control | Links |
|---|---|---|
| Bilophila | ||
| Bilophila wadsworthia | ||
| Bacteroides stercoris |
Revision editor(s): Joiejoie
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