Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2025; 17(3): 101991
Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.101991
Irreversible electroporation combined with anti-programmed cell death protein 1 therapy promotes tumor antigen-specific CD8+ T cell response
Yang-Yang Ma, Xiao-Hua Wang, Jian-Ying Zeng, Ji-Bing Chen, Li-Zhi Niu
Yang-Yang Ma, Xiao-Hua Wang, Jian-Ying Zeng, Ji-Bing Chen, Central Laboratory, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
Li-Zhi Niu, Department of Oncology, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
Author contributions: Ma YY wrote the paper; Wang XH and Zeng JY performed the study selection; Chen JB analyzed the data; Niu LZ designed the project and edited the manuscript; All authors reviewed the final manuscript.
Supported by Science and Technology Program of Guangzhou, No. 202102010077; and International Science Foundation of Guangzhou Fuda Cancer Hospital, No. Y2020-ZD-03.
Institutional animal care and use committee statement: This animal experiment was examined and approved by the laboratory animal welfare ethics committee of the Jinan University.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
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, MAMS, MD, PhD, Chief Physician, Department of Oncology, Guangzhou Fuda Cancer Hospital, No. 2 Tangde West Road, Tianhe District, Guangzhou 510665, Guangdong Province, China. niuboshi@fudahospital.com
Received: October 4, 2024
Revised: November 21, 2024
Accepted: January 8, 2025
Published online: March 15, 2025
Processing time: 133 Days and 6.8 Hours
Abstract
BACKGROUND

Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to activate the host’s immune system. However, this approach is insufficient to prevent cancer progression, and complementary approaches are required for effective immunotherapy.

AIM

To assess the immunomodulatory effects and mechanism of IRE combined anti-programmed cell death protein 1 (PD-1) treatment in subcutaneous pancreatic cancer models.

METHODS

C57BL-6 tumor-bearing mice were randomly divided into four groups: Control group; IRE group; anti-PD-1 group; and IRE + anti-PD-1 group. Tumor-infiltrating T, B, and natural killer cell levels and plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-α) were evaluated. Real-time PCR was used to determine the expression of CD8 (marker of CD8+ T cells) in tumor tissues of the mice of all groups at different points of time. The growth curves of tumors were drawn.

RESULTS

The results demonstrated that the IRE + anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration, including CD4+ and CD8+ T cells compared with the control group. Additionally, the IRE + anti-PD-1 group showed increased infiltration of natural killer and B cells, elevated cytokine levels, and higher CD8 mRNA expression. Tumor volume was significantly reduced in the IRE + anti-PD-1 group, indicating a more pronounced therapeutic effect.

CONCLUSION

The combination of IRE and anti-PD-1 therapy promotes CD8+ T cell immunity responses, leading to a more effective reduction in tumor volume and improved therapeutic outcomes, which provides a new direction for ablation and immunotherapy of pancreatic cancer.

Keywords: Irreversible electroporation; Pancreatic cancer; Programmed cell death protein 1 blockade; CD8+ T cell; Anticancer immunity

Core Tip: This study highlighted the synergistic effect of combining irreversible electroporation with anti-programmed cell death protein 1 therapy in the treatment of subcutaneous pancreatic cancer. The combination significantly enhanced T lymphocyte infiltration, elevated key cytokine levels, and promoted CD8+ T cell-mediated immune responses, resulting in a marked reduction in tumor volume. These findings suggest a promising avenue for improving immunotherapy strategies in pancreatic cancer through enhanced local tumor ablation methods.