通过靶向 T 细胞和 NK 细胞提高溶瘤病毒癌症治疗疗效的潜在策略

Oncolytic viruses (OVs) elicit potent tumor lysis and remodel the tumor microenvironment (TME) to activate adaptive and innate immunity, yet their efficacy depends critically on T and NK cell responses.

Here, we review recent advances in the characterization and engineering of OVs to enhance lymphocyte-mediated tumor control. CD8⁺ cytotoxic T cells and CD4⁺ helper T cells drive durable antitumor immunity through OV-enhanced antigen presentation, memory formation, and modulation of Tregs, whereas T cell exhaustion and checkpoint interactions remain key barriers.

Arming OVs with cytokines, chemokines, bispecific engagers, or metabolic modulators enhances effector T-cell expansion, infiltration, and cytotoxicity in solid tumors. In parallel, NK cells-whose efficacy is often limited by poor intratumoral activity and antiviral competition-are increasingly harnessed by OV platforms expressing immune stimulators or checkpoint modulators. Combination strategies with targeted therapies, checkpoint blockade, or adoptive NK/T cell transfer further potentiate therapeutic efficacy.

Importantly, although OVs may inadvertently amplify dominant antiviral responses at the expense of antitumor activity, strategies incorporating tumor antigen encoding and TME reprogramming can overcome this limitation. Collectively, these findings underscore the central role of T and NK cells in OV-based immunotherapy and highlight rational arming and combination approaches to improve tumor control and long-term protection.