Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade |
| |
| Authors: | Yang Liu Jing Cai Wenfeng Liu Yuan Lin Li Guo Xincheng Liu Zhen Qin Cuiying Xu Yanming Zhang Xingwen Su Kai Deng Guangmei Yan Jiankai Liang |
| |
| Institution: | 1.Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China ;2.Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China ;3.Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China |
| |
| Abstract: | Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8+ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.Subject terms: Cancer microenvironment, Targeted therapies |
| |
| Keywords: | |
|
|
