Oncolytic virus and immunogenic cell death in cancer therapy
GuoXiu Cao, Chan Ding, Jun Dai, Xusheng Qiu
Abstract
As a promising cancer treatment strategy, oncolytic viruses (OVs) selectively replicate and kill tumor cells while sparing normal cells. They improve the tumor immunosuppressive microenvironment through multiple mechanisms, including direct infection, replication, and lysis of tumor cells—leading to the release of tumor-associated antigens (TAAs), chemokines, and cytokines, which in turn induce immunogenic cell death (ICD) and trigger sustained antitumor immune responses. Currently, while OVs have demonstrated therapeutic efficacy in multiple preclinical and clinical studies, their monotherapy fails to benefit a broad spectrum of cancer patients. Therefore, there remains a need to fully understand the biological mechanisms of OVs and optimize immunotherapeutic strategies to benefit more cancer patients and enhance therapeutic efficacy. In this review, we discuss how the immune responses induced by OVs maintain a balance between antiviral and antitumor immunity, as well as their unique characteristics in inducing ICD. In addition, we describe how to enhance the efficacy of cancer immunotherapy by combining OVs therapy with ICD inducers, aiming to provide valuable insights to guide the development of clinical OVs -based therapies. a | OVs selectively infect and replicate in tumor cells while sparing normal cells, modulate the balance between antiviral and antitumor responses, and release tumor-associated antigens to recruit innate effector cells. b | In lymph nodes, oncolytic viruses and immunogenic cell death inducers promote the presentation of tumor antigens to naive and memory T cells. c | After infiltrating tumor sites, activated T cells recognize tumor antigens, induce immunogenic cell death, and thereby maximize tumor cell elimination. • Oncolytic viruses selectively infect tumor cells while sparing normal cells; • Oncolytic viruses evolve multiple mechanisms to induce immunogenic cell death; • Engineering oncolytic viruses as potential methods for enhancing antitumor efficacy; • Oncolytic viruses combined with immunogenic cell death inducers are potential antitumor therapy.