Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy-induced colitis.

Molecular oncology 2022 Apr

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Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs). In responders, genes related to DNA repair and cell cycle signatures were enriched in responders whereas signatures related to innate immune response, NFAT and IFN-γ signaling pathways were enriched in nonresponders. Gut microbial composition revealed an association between moderate GI irAE and favorable response to ICI therapy. Favorable therapeutic responses to ICI and GI irAE treatments were associated with taxa classified as Enterobacteriaceae and were related to ribonucleoprotein complex biogenesis, cytokine-mediated signaling pathway, tRNA metabolic process, and ribonucleoprotein complex assembly in the colon. These findings open new perspectives for improving the efficacy and safety of cancer immunotherapy. © 2021 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Citation

Toshiharu Sakurai, Marco A De Velasco, Kazuko Sakai, Tomoyuki Nagai, Hiroki Nishiyama, Kentaro Hashimoto, Hirotsugu Uemura, Hisato Kawakami, Kazuhiko Nakagawa, Hiroyuki Ogata, Kazuto Nishio, Masatoshi Kudo. Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy-induced colitis. Molecular oncology. 2022 Apr;16(7):1493-1507