Oncolytic virotherapy: Sparking durable anti-tumor immunity through microenvironment modulation.

Oncolytic virotherapy (OVT) is a novel approach to cancer treatment that utilizes viruses to infect and destroy tumor cells selectively. Beyond direct oncolysis, OVT significantly reshapes the tumor microenvironment (TME), activating the adaptive immune system to generate robust and durable anti-tumor immunity. This review examines the diverse mechanisms by which OVT modulates the TME, including physical remodeling, alterations in cellular composition, and the induction of immunogenic cell death, which releases antigens and adjuvants that enhance immune activation. We also explore the synergistic effects of combining OVT with immune checkpoint inhibitors to counteract the immunosuppressive TME. Additionally, recent clinical studies are highlighted, demonstrating the transition of 'cold' tumors to 'hot' tumors and the establishment of systemic tumor control in patients treated with OVT. By enhancing TME immunogenicity, OVT emerges as a potent adjunct to anti-tumor immunotherapies, offering new opportunities to overcome resistance and achieve better therapeutic outcomes.