PD59-12: Microwave Ablation Combined with Anti-PD-1/CTLA-4 Therapy Induces Anti-Tumor Immune Response to Renal Cell Carcinoma in a Murine Model

Run-Qi GUO*, Jin-Zhao PENG, Xiao-Guang LI, Beijing, China, People's Republic of

Introduction: Our current study was designed to investigate the characteristics of immune responses induced by MWA and dual immune checkpoint inhibitors (ICIs) in tumor tissues from tumor-bearing mice, with purpose of providing new insight into immune suppressive mechanisms limiting MWA efficacy and exploring the potential of dual ICIs in combination with MWA in cancer therapy.

Methods: First, untreated tumor assessment was performed to determine whether untreated tumor growth was suppressed. Mice with tumors established on the left kidney and right flank were randomly divided into 4 groups: the control group, the MWA group, the ICI group, and the MWA+ ICI group. Then, a rechallenge test was performed to determine whether systemic anti-tumor immunity was established.

Results: Although the volume of the untreated tumors continued to increase, tumor growth rates in the ICI group and the MWA+ICI group were significantly lower. CD8+ T cells were only significantly higher in the MWA+ICI group, while Treg cells were significantly lower in the MWA group, the ICI group and the MWA+ICI group. The MWA+ICI group also showed the highest amount of IFN-?. Histopathologic studies revealed that cytotoxic T lymphocyte-associated antigen 4 expression (CTLA-4) in the distant tumor was significantly lower in the ICI group and the MWA+ICI group. MWA treatment led to an increase in programmed death ligand 1 (PD-L1)/ programmed death receptor 1 (PD-1) expression; however, after combining with ICI treatment, the expression decreased.

In the tumor rechallenge test, tumor rejection was apparent in 16.7% of the mice in the MWA group, 50% of the mice in the ICI group, and 66.7% of the mice in the MWA+ICI group, whereas no mice in the control group showed tumor rejection.

Conclusions: This study demonstrated that MWA induced systemic anti-tumor immunity was enhanced by combined use of anti PD-1/CTLA-4 therapy in a murine RENCA tumor model. The mice that received the combination therapy showed suppression of untreated tumor growth and tumor rejection. This treatment regimen is a potential clinical approach to enhance systemic anti-tumor immunity in patients with metastatic renal cell carcinoma.

Source of Funding: This study was supported by Beijing Hospital Scientific Research Starting Foundation for PhD/MD under Grant BJ-2019-135 to Dr. Guo.