Enhancing cancer immunotherapy: The role of CAR-T cells and oncolytic viruses in modulating tumor microenvironment

Cancer immunotherapy has revolutionized oncology by improving therapeutic specificity and efficacy, leading to major clinical successes. Among these approaches, chimeric antigen receptor (CAR-T) cell therapy has shown remarkable results in hematological malignancies. However, its effectiveness in solid tumors is limited by antigen heterogeneity, poor tumor infiltration, and the immunosuppressive tumor microenvironment (TME). To address these limitations, combining CAR-T therapy with oncolytic viruses (OVs) has gained increasing attention. OVs selectively infect and lyse tumor cells while simultaneously stimulating innate and adaptive antitumor immune responses through enhanced antigen release and inflammatory signaling, thereby modulating the TME and enhancing antigen presentation. Evidence from preclinical studies and early clinical trials indicates that CAR-T and OV combination therapy can generate synergistic antitumor effects by improving immune cell infiltration, enhancing cytotoxic activity, and reducing immune evasion. This review highlights recent Advances in the engineering of CAR-T cells and OVs and their synergistic potential in the treatment of solid tumors.