Reovirus combined with a STING agonist enhances anti-tumor immunity in a mouse model of colorectal cancer

• Published in: Cancer Immunology, Immunotherapy Vol. 72; no. 11; pp. 3593 - 3608
• Main Authors: Sugimura, Naomi, Kubota, Eiji, Mori, Yoshinori, Aoyama, Mineyoshi, Tanaka, Mamoru, Shimura, Takaya, Tanida, Satoshi, Johnston, Randal N., Kataoka, Hiromi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2023; Springer Nature B.V
• Subjects: Agonists; Animals; Antigen (tumor-associated); Antitumor activity; Apoptosis; Cancer Research; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - therapy; Cytokines; Cytotoxicity; Immunity, Innate; Immunology; Immunotherapy; Innate immunity; Interferon; Interferon Type I - metabolism; Lymphocytes T; Lysis; Mammals - metabolism; Medicine; Medicine & Public Health; Mice; Oncology; Oncolysis; Reoviridae - metabolism; RNA viruses; Tumor cells; Tumor Microenvironment; Tumors; STING agonist; Reovirus; Colorectal cancer
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-023-03509-0

Reovirus, a naturally occurring oncolytic virus, initiates the lysis of tumor cells while simultaneously releasing tumor antigens or proapoptotic cytokines in the tumor microenvironment to augment anticancer immunity. However, reovirus has developed a strategy to evade antiviral immunity via its inhibitory effect on interferon production, which negatively affects the induction of antitumor immune responses. The mammalian adaptor protein Stimulator of Interferon Genes (STING) was identified as a key regulator that orchestrates immune responses by sensing cytosolic DNA derived from pathogens or tumors, resulting in the production of type I interferon. Recent studies reported the role of STING in innate immune responses to RNA viruses leading to the restriction of RNA virus replication. In the current study, we found that reovirus had a reciprocal reaction with a STING agonist regarding type I interferon responses in vitro; however, we found that the combination of reovirus and STING agonist enhanced anti-tumor immunity by enhancing cytotoxic T cell trafficking into tumors, leading to significant tumor regression and survival benefit in a syngeneic colorectal cancer model. Our data indicate the combination of reovirus and a STING agonist to enhance inflammation in the tumor microenvironment might be a strategy to improve oncolytic reovirus immunotherapy.