Microwave ablation combined with anti-PD-1 therapy enhances systemic antitumor immunity in a multitumor murine model of Hepa1-6

Abstract

Background To evaluate the changes of immune environment of distant tumors after combined microwave ablation (MWA) and anti- programmed death receptor − 1 (anti-PD-1) therapy, and assess the changes of systemic immune response. Methods Bilateral hepatocellular carcinoma model was established in mice, which were then subsequently treated with MWA, or anti-PD-1, or no treatment, or MWA + anti-PD-1. The contralateral tumor volume and mice survival time were recorded. Flow cytometry and immunohistochemistry were used for evaluation of the immune cells subgroup change of contralateral tumor. In addition, tumor rechallenge tests were conducted on unilateral tumor-bearing mice to examine the systemic immune effects of the combination therapy. Results We found that MWA treatment alone failed to produce a significant abscopal effect. In contrast, the combination group had longer survival than the MWA or anti-PD-1 group alone, with slower distant tumor growth. Moreover, the tumor-specific immune responses induced by combination therapy are stronger than anti-PD-1 or MWA alone. Combination therapy also elevated the levels of Th1-type cytokines in peripheral blood. In addition, after tumor rechallenge, the combination group showed more rejection to the reimplanted tumors (6 out of 10 mice). Conclusions The combination of MWA and anti-PD-1 therapy resulted in the inhibition of distant tumor growth and the construction of a systemic anti-tumor immune environment that can reduce recurrence.