High-resolution metagenomic profiling revealed gut microbiome features for the response to cancer immunotherapy reproducible among multiple cohorts of patients.

Cancer immunotherapy is currently standard of treatment showing significant clinical benefits to cancer patients, but the beneficial effects are limited to a relatively small subset of patients. Of various factors that may affect the efficacy of cancer immunotherapy, the gut microbiome is receiving more attention because of its strong correlation with immune regulation. Recently, independent studies based on Western populations have identified several taxa that are differentially abundant between responders and nonresponders. However, the reported taxa associated with anti-PD-1 response differ entirely among these studies. In this study, we performed 1) deep (u003e100M reads in average) metagenome shotgun sequencing on the fecal sample of 49 Korean non-small cell lung cancer (NSCLC) patients, 2) taxonomic profiling using a highly comprehensive gut microbiome-specific genome database, and 3) gene-level profiling with the gut microbiome specific gene catalog to improve the resolution of metagenomic analysis. With the high-resolution metagenomic profiling, we found several taxonomic and functional signatures associated with the response of anti-PD-1 therapy. Interestingly, we found that some of the signatures were reproduced in five independent datasets regardless of the cancer types (melanoma, NSCLC, and renal cell carcinoma) and the type of immunotherapy (anti-PD-1, anti-CTLA4, and the combination of them). For instance, a responder-enriched taxon in the Korean cohort was more frequently detected in the responders in all cohorts (abundance fold-change u003e 2) and significantly enriched (p Citation Format: Chan Yeong Kim, Beung-Chul Ahn, Min Hee Hong, Yoo Jin Chun, Hye Ryun Kim, Insuk Lee. High-resolution metagenomic profiling revealed gut microbiome features for the response to cancer immunotherapy reproducible among multiple cohorts of patients [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B16.