Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages.

Intratumoral administration is a widely used method for oncolytic virotherapy, as it enables immediate access of virus particles to the target tumor and potentially lead to the suppression of untreated distant tumors via in situ vaccination. However, because the injection volume and concentration of the virus solution are physically limited, the dose level cannot be increased. Additionally, efficacy in distant tumors needs improvement to prolong patient survival. Here, we demonstrate the benefit of oxaliplatin, with detailed mechanisms revealed through transcriptome analysis, which may provide a solution for the crucial deficiencies of oncolytic virotherapy. In virus-injected tumors, oxaliplatin improved virus retention through suppression of type I interferons. In distant virus-naive tumors, oxaliplatin induced alterations in the intratumoral macrophage characteristics, leading to the chemotaxis and recruitment of activated T cells and subsequently inducing an inflammatory state in the non-injected tumors. Our findings can be a trigger to change the therapeutic paradigm of oncolytic virotherapy for patients with systemic metastases.