34954 Cutaneous microbial markers of squamous cell carcinoma risk in solid organ transplant recipients

Abstract

Solid organ transplant recipients (SOTRs) are 100-times more prone to aggressive cutaneous squamous cell carcinoma (SCC) compared with the general population. Despite this increased mortality, our ability to prognosticate risk of cancer in SOTRs is still poor. Accumulating evidence suggests a detrimental influence of microbial dysbiosis on transplant outcomes and immunosuppressant metabolism. Additionally, altered skin microbiome, specifically excessive colonization of the skin by Staphylococcus aureus, has been found in cutaneous SCCs of immunocompetent individuals. We hypothesized that cutaneous dysbiosis is a potential modifier to the risk of SCC in SOTRs and that the microbiome of SOTRs with a history of SCC (>4 instances) is distinct from the microbiome of SOTRs without a history of SCC. To investigate this theory, we generated microbial genomic data from the skin samples of 2 matched cohorts: SOTRs with and without history of SCC. Analyses included testing for differences in microbial diversity measures and differentially relatively abundant microbiome species between cohorts. In the cutaneous microbiomes of SOTRs with SCC history, we identified a significantly reduced abundance of Roseomonas mucosa, which is a S aureus–suppressive species. This suggests a protective effect of R mucosa against the development of SCC through suppression of a bacterial species hypothesized to initiate inflammation-related signaling involved in SCC-genesis. Overall, these findings not only point to a potential role of cutaneous microbiomes as predictive biomarkers for the development of SCC in SOTRs but also suggest that the microbiome can be used for potential preventive and interventional strategies.