The role and mechanism of neutrophils in oncolytic virus therapy

Oncolytic viruses (OVs) are a class of viruses capable of specifically infecting and killing tumor cells. They exert antitumor effects through direct lysis of tumor cells, activation of the immune system, and disruption of tumor vasculature. Neutrophils, which originate from the bone marrow, are the most abundant leukocytes in peripheral blood and the immune system and play a dual regulatory role in oncolytic virotherapy. In different TME, neutrophils can polarize into two phenotypes: N1 and N2. N1 neutrophils, owing to their chemotaxis and tumor-homing capabilities, can serve as delivery vehicles for OVs, enhance the therapeutic efficacy of oncolytic virotherapy, and activate host immune responses. In contrast, N2 neutrophils impair the efficacy of OVs through their antiviral activity and immunosuppressive functions. Therefore, an in-depth understanding of the mechanisms underlying the role of neutrophils in oncolytic virotherapy is of great significance for optimizing OV-based therapies and improving their clinical application outcomes.