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

Autor: Lee WS; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea., Lee SJ; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea., Lee HJ; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea., Yang H; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea., Go EJ; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea., Gansukh E; Virocure Inc., Seoul, Republic of Korea., Song KH; Virocure Inc., Seoul, Republic of Korea., Xiang X; Department of Biochemistry, Microbiology, and Immunology, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada., Park DG; Virocure Inc., Seoul, Republic of Korea.; Department of Surgery, School of Medicine, Dankook University, Cheonan, Republic of Korea., Alain T; Department of Biochemistry, Microbiology, and Immunology, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada., Chon HJ; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. minidoctor@cha.ac.kr.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. minidoctor@cha.ac.kr., Kim C; Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. chan@cha.ac.kr.; Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. chan@cha.ac.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 22; Vol. 15 (1), pp. 9092. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1038/s41467-024-53347-6
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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