Gut microbiome features associate with immune checkpoint inhibitor response in individuals with non-melanoma skin cancers: an exploratory study

February 27, 2025

Journal

Microbiology Spectrum

Publication Date

February 27, 2025

Authors

Zhao Y, Ferri J, White J, Schollenberger M, Peloza K, Sears C, Lipson E, Shaikh F

Merkelcell.org Summary

Scientists are studying how the gut microbiome – the community of tiny organisms in our intestines – affects skin cancer patients receiving immunotherapy (a drug that helps the immune system fight cancer). While factors like exercise and a high-fiber diet may help create a healthier gut and improve treatment, we don’t fully understand how the microbiome influences immunotherapy response in Merkel cell carcinoma (MCC).

In this unique study, researchers at Johns Hopkins University analyzed stool samples from 21 patients who received immunotherapy for their advanced skin cancers, including MCC (5 patients), squamous cell carcinoma (SCC; 11 patients), and basal cell carcinoma (5 patients). They found that SCC patients who responded well to immunotherapy had different gut bacteria with different activity compared to those who didn’t. However, the results for MCC remain unclear, partly because there were too few MCC patients in the study. These findings suggest that the gut microbiome may play a role in immunotherapy success, but larger studies are needed to better understand its impact on MCC treatment.

Our Seattle MCC team is excited to explore similar research with our patients. Stay tuned for updates and opportunities to get involved!

Abstract

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.
View the clinical publication