Oncolytic virus and immunogenic cell death in cancer therapy

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.