Anti-PD-1 blockade reverses low-intensity electric stimulation-driven pancreatic cancer progression

Sep 23, 2026

Irreversible electroporation (IRE) can generate uneven electric fields, leaving some pancreatic ductal adenocarcinoma (PDAC) cells exposed to low-intensity electric stimulation (LIES). This study established orthotopic PDAC models to characterize immune microenvironment changes after LIES and assessed combined therapy with anti-PD-1 blockade. In vitro and in vivo analyses showed that anti-PD-1 blockade reversed LIES-driven tumor progression and enhanced CD8+ T cell activation. Mechanistically, LIES activated the JAK2–STAT3 pathway and induced PD-L1 expression in PDAC cells.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Background and Rationale

Methods

In vivo model and treatment

In vitro assays

Immune profiling and sequencing

Results

Model establishment and immune modulation

Effects on tumor growth and responses

Pathway and PD-L1 regulation

Conclusions

Keywords

TYPE Original Research PUBLISHED 19 May 2026 DOI 10.3389/fimmu.2026.1793161 OPEN ACCESS EDITED BY Gaurisankar Sa, Bose Institute, India REVIEWED BY Zhuozhuo Wu, Shanghai Jiao Tong University, China Sarah Mansouri, Universite´ de Sherbrooke, Canada *CORRESPONDENCE Shengping Li [lishengp@mail.sysu.edu.cn](lishengp@mail.sysu.edu.cn)[ ](lishengp@mail.sysu.edu.cn)Chaobin He [hechb@sysucc.org.cn](hechb@sysucc.org.cn) †These authors have contributed equally to this work RECEIVED 21 January 2026 REVISED 24 April 2026 ACCEPTED 30 April 2026 PUBLISHED 19 May 2026 CITATION Jiang L, Li X, Zeng D, Xi P, Yao Z, Zhu Q, Lian S, Li S and He C (2026) Anti-PD-1 blockade reverses low-intensity electric stimulation-driven pancreatic cancer progression. Front. Immunol. 17:1793161 . doi: 10.3389/fimmu.2026.1793161 COPYRIGHT © 2026 Jiang, Li, Zeng, Xi, Yao, Zhu, Lian, Li and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Anti-PD-1 blockade reverseslow-intensity electric stimulation-driven pancreatic cancer progression Lingmin Jiang 1†, Xiyuan Li 2†, Dejun Zeng 3†, Pu Xi 4†, Zehui Yao 1†, Qi Zhu 1, Shaopu Lian 1, Shengping Li 1* and Chaobin He 1* 1 Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, 2 Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, 3 Department of General Surgery, Pingshan District Central Hospital of Shenzhen, Shenzhen, China, 4 Department of Head Neck and Thyroid, The Afﬁliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China Background: Irreversible electroporation (IRE) represents a potential therapeutic approach for pancreatic ductal adenocarcinoma (PDAC) . However, differences in tumor size and shape can lead to an uneven distribution of the electric ﬁeld, causing certain cells to receive only low-intensity electric stimulation (LIES) . This study aimed to explore the tumor immune microenvironment following LIES and evaluate the synergistic antitumor effects of LIES combined with anti-PD- 1 blockade. Methods: Orthotopic PDAC models in mice were treated with LIES with or without anti-PD-1 blockade. In vitro assays under varying electric ﬁelds assessed tumor cell viability, migration, and epithelial-mesenchymal transition (EMT) . Tumor immune microenvironment remodeling was comprehensively proﬁled using ﬂow cytometry, multicolor immunoﬂuorescence, and single-cell RNA sequencing (sc RNA-seq) . The underlying mechanism was further investigated via bulk RNA sequencing and validated in vitro. Results: Orthotopic PDAC models were established and utilized for the ﬁrst time to evaluate the immune modulation and macrophage polarization effects of LIES. Cell-based assays were conducted to assess the impact of varying ﬁeld strengthson cell proliferation and migration. Anti-PD-1 blockade reversed the tumor growth and systemic antitumor responses following the LIES. Flow cytometry, multicolor immunoﬂuorescence, and scRNA-seq revealed that combination therapy ampliﬁed CD8+ T cell activation. Further bulk RNA-seq analysis revealed that LIES activated the JAK2-STAT3 pathway, inducing expression of PD-L1 in PDAC cells. Conclusions: Anti-PD-1 blockade can reverse LIES-driven t

FAQs

What is the key problem addressed by combining LIES/IRE with anti-PD-1 blockade?

Electric field heterogeneity during IRE can expose PDAC cells to LIES, leading to incomplete control and tumor progression. Anti-PD-1 blockade was tested to counteract this progression and immune suppression.

How were immune changes after LIES characterized?

Tumor immune microenvironment remodeling was profiled using flow cytometry, multicolor immunofluorescence, and single-cell RNA sequencing (scRNA-seq), with additional bulk RNA sequencing for mechanism support.

What mechanism links LIES to PD-L1 expression in PDAC cells?

LIES activated the JAK2–STAT3 pathway, which induced PD-L1 expression in PDAC cells, providing a basis for how anti-PD-1 can reverse tumor-promoting effects.

Sep 23, 2026

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