Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy‐induced colitis. Issue 7 (28th July 2021)

• Record Type: Journal Article
• Authors: Sakurai, Toshiharu; De Velasco, Marco A; Sakai, Kazuko; Nagai, Tomoyuki; Nishiyama, Hiroki; Hashimoto, Kentaro; Uemura, Hirotsugu; Kawakami, Hisato; Nakagawa, Kazuhiko; Ogata, Hiroyuki; Nishio, Kazuto; Kudo, Masatoshi
• Is Part Of: Molecular oncology. Volume 16:Issue 7(2022)
• Page Start: 1493
• Page End: 1507
• Publication Date: 2021-07-28
• Subjects: Enterobacteriaceae -- gastrointestinal immune‐related adverse event -- immune checkpoint -- integrative analysis -- microbiome -- whole transcriptome; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13062
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : In our study, we used an integrative approach to investigate the relationships between mucosal gene expression and microbial composition in patients with cancer that display gastrointestinal immune‐related adverse events (GI‐irAE) after immune checkpoint inhibitor (ICI) therapy. We clustered patients according to their clinical characteristics and identified relevant features associated with response to ICI in inflamed mucosa. Our research indicates that both the host cell transcriptome and the gut microbiome play a key role in immunotherapy‐induced colitis in patients with cancer.