Oral reovirus reshapes the gut microbiome and enhances antitumor immunity in colon cancer

Won Suk Lee, Seung Joon Lee, Hye Jin Lee, Hannah Yang, Eun-Jin Go, Enkhtaivan Gansukh, Ki-Hoon Song, Xiao Xiang, Dong Guk Park, Tommy Alain, Hong Jae Chon () and Chan Kim ()
Additional contact information
Won Suk Lee: CHA University
Seung Joon Lee: CHA University
Hye Jin Lee: CHA University
Hannah Yang: CHA University
Eun-Jin Go: CHA University
Enkhtaivan Gansukh: Virocure Inc.
Ki-Hoon Song: Virocure Inc.
Xiao Xiang: University of Ottawa
Dong Guk Park: Virocure Inc.
Tommy Alain: University of Ottawa
Hong Jae Chon: CHA University
Chan Kim: CHA University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The route of oncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity. Oral reovirus treatment shows no gross toxicities and effectively suppresses multifocal tumor lesions. Orally administered reovirus interacts with the host immune system in the Peyer’s patch of the terminal ileum, increases IgA+ antibody-secreting cells in the lamina propria through MAdCAM-1+ blood vessels, and reshapes the gut microbiome. Oral reovirus promotes antigen presentation, type I/II interferons, and T cell activation within distant tumors, but does not reach or directly infect tumor cells beyond the gastrointestinal tract. In contrast to intratumoral reovirus injection, the presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are indispensable for orally administered reovirus-induced antitumor immunity. Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.

Date: 2024
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DOI: 10.1038/s41467-024-53347-6

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