Irreversible electroporation combined with checkpoint blockade stimulates antitumor immune response in a hepatocellular carcinoma mouse model

doi:10.4251/wjgo.v17.i9.110166

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Sep 15, 2025 (publication date) through Sep 15, 2025

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastrointest Oncol. Sep 15, 2025; 17(9): 110166
Published online Sep 15, 2025. doi: 10.4251/wjgo.v17.i9.110166

Irreversible electroporation combined with checkpoint blockade stimulates antitumor immune response in a hepatocellular carcinoma mouse model

Yan-Li Xing, Hong-Mei Li, Xiao-Ming Pang, Ying Zhang, Ting Yang, Yan-Hong Li, De-Chuan Liu, Yang-Yang Ma, Li-Zhi Niu

Yan-Li Xing, Hong-Mei Li, Xiao-Ming Pang, Ying Zhang, Ting Yang, De-Chuan Liu, Li-Zhi Niu, Department of Oncology, Guangzhou Fuda Cancer Hospital, Jinan University, Guangzhou 510655, Guangdong Province, China

Yan-Hong Li, Department of Nursing, Guangzhou Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China

Yang-Yang Ma, Central Laboratory, Guangzhou Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China

Co-corresponding authors: Yang-Yang Ma and Li-Zhi Niu.

Author contributions: Xing YL wrote the paper; Li HM, Pang XM, Zhang Y, Yang T, Li YH and Liu DC performed the study selection; Ma YY analyzed the data; Niu LZ designed the project and edited the manuscript; All authors reviewed the final manuscript.

Supported by the Science and Technology Program of Guangzhou, No. 202201020024.

Institutional review board statement: This study does not involve any human experiments.

Institutional animal care and use committee statement: Female C57BL/6 mice were housed in a specific pathogen-free facility (12-hour light/dark cycle, 22 ± 2 °C, 50% ± 10% humidity) with ad libitum access to food and water. Mice meeting any endpoint criterion were euthanized via carbon dioxide overdose followed by cervical dislocation. All procedures involving animals were reviewed and approved by the Medical Ethics Committee of Guangzhou Fuda Cancer Hospital (No. FD-IRB-SL-KY-20230829).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The data are available from the corresponding author at niuboshi@fudahospital.com.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Li-Zhi Niu, PhD, Professor, Department of Oncology, Guangzhou Fuda Cancer Hospital, Jinan University, No. 2 Tangde West Road, Tianhe District, Guangzhou 510665, Guangdong Province, China. niuboshi@fudahospital.com

Received: June 4, 2025
Revised: July 5, 2025
Accepted: August 15, 2025
Published online: September 15, 2025
Processing time: 108 Days and 2.2 Hours

Abstract

BACKGROUND

Irreversible electroporation (IRE) represents an innovative localized technique for tumor ablation, possessing the capacity to activate the immune response of the host. However, this method alone is inadequate to halt cancer progression, necessitating the integration of additional strategies to achieve effective immunotherapy.

AIM

To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1 (PD-1) therapy within a murine model of hepatocellular carcinoma.

METHODS

C57BL-6 mice with tumor growth were divided into four separate cohorts: Control group; IRE group; Anti-PD-1 group; And IRE + anti-PD-1 group. The infiltration levels of T, B, and natural killer cells within the tumors, as well as the plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-β), were evaluated. Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation (CD) 8 (a marker indicative of CD8⁺ T cells) in the tumor specimens of the mice at various temporal intervals. Tumor growth trajectories were charted.

RESULTS

The results indicated that the IRE + anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration, particularly CD4⁺ and CD8⁺ T cells, when compared to the control cohort. Additionally, this group displayed increased infiltration of natural killer and B cells, augmented cytokine levels, and elevated CD8 messenger RNA expression. A marked decrease in tumor volume was noted in the IRE + anti-PD-1 group, indicating enhanced therapeutic efficacy.

CONCLUSION

The combined application of IRE and checkpoint blockade elicits an antitumor immune response, leading to a more substantial reduction in tumor volume and improved therapeutic outcomes, thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.

Keywords: Irreversible electroporation; Hepatocellular carcinoma; Programmed cell death protein 1 blockade; Cluster of differentiation 8⁺ T cell; Anticancer immunity

Core Tip: This study highlights the combination of irreversible electroporation and anti-programmed cell death protein 1 therapy synergistically enhances antitumor immunity by significantly increasing tumor infiltration of T cells [cluster of differentiation (CD) 4⁺, CD8⁺], natural killer cells, and B cells, elevating Th1-associated cytokine levels (interleukin-2, interferon-γ, and tumor necrosis factor-β), and upregulating CD8 messenger RNA expression. This dual approach markedly reduces tumor volume compared to monotherapies, demonstrating potentiated therapeutic efficacy and providing a novel strategy for ablation-immunotherapy integration, with potential implications for hepatocellular carcinoma.