Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy

Author:

Liao Changli12,Zhang Guiyuan1,Huang Ruotong3,Zeng Linyuan1,Chen Bin1,Dai Haitao1,Tang Keyu1,Lin Run1,Huang Yonghui1

Affiliation:

1. Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan 2nd Road, Guangzhou 510080, China

2. Department of Interventional Therapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55 South Renmin Road, Section 4, Chengdu 610041, China

3. Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK

Abstract

Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8+ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes.

Funder

Natural Science Foundation of Guangdong Province

Guangzhou Municipal Science and Technology Program

National Natural Science Foundation of China

Basic and Applied Basic Research Foundation of Guangdong Province

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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