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Li JQ, Zhao HG, Cai HQ. Epigenetic-immune landscape of pancreatic ductal adenocarcinoma: From tumor biology to multimodal treatment in the surgical setting. World J Gastrointest Surg 2026; 18(11): 125757 [DOI: 10.4240/wjgs.125757]
World J Gastrointest Surg. Nov 27, 2026; 18(11): 125757 Published online Nov 27, 2026. doi: 10.4240/wjgs.125757
Epigenetic-immune landscape of pancreatic ductal adenocarcinoma: From tumor biology to multimodal treatment in the surgical setting
Jun-Qi Li, Hong-Guang Zhao, Hong-Qiao Cai
Jun-Qi Li, Hong-Qiao Cai, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Hong-Guang Zhao, Department of General Surgery, Changchun Children’s Hospital, Changchun 130000, Jilin Province, China
Author contributions: Li JQ contributed to the discussion and design of the manuscript; Zhao HG contributed to the writing and editing of the manuscript, and review of the literature; Cai HQ designed the overall concept and outline of the manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Hong-Qiao Cai, MD, PhD, Associate Professor, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130021, Jilin Province, China. hongqiaocai@jlu.edu.cn
Received: July 16, 2026 Revised: August 14, 2026 Accepted: September 18, 2026 Published online: November 27, 2026 Processing time: 119 Days and 23.3 Hours
Abstract
Pancreatic cancer, one of the most lethal malignancies, is characterized by aggressive progression, late diagnosis, and resistance to conventional therapies. Increasing evidence indicates that epigenetic alterations contribute not only to tumor progression but also to immune regulation. These epigenetic alterations regulate immune cell differentiation, infiltration, and function, thereby promoting the formation of an immunosuppressive tumor microenvironment. This narrative minireview aims to summarize the current understanding of epigenetic-immune crosstalk in pancreatic ductal adenocarcinoma and discuss its potential implications for translational research and future therapeutic development. Various epigenetic-immune interactions regulate immune checkpoints, macrophages, myeloid-derived suppressor cells, and regulatory T cells, collectively contributing to immune evasion. Combinations of epigenetic modulators and immune checkpoint inhibitors are emerging, particularly in the surgical setting. They hold promise for restoring anti-tumor immunity and overcoming resistance. This article provides an overview of epigenetic-immune crosstalk in pancreatic cancer, with implications for novel therapies in the surgical setting. However, current evidence remains predominantly preclinical, and prospective studies are warranted.
Core Tip: This article highlights the important interplay between epigenetic alterations and the immune microenvironment. We summarize the roles of DNA methylation, histone modification, and non-coding RNAs in regulating immune checkpoints, macrophages, myeloid-derived suppressor cells, and regulatory T cells, all of which contribute to an immunosuppressive tumor microenvironment. We also discuss therapies combining epigenetic modulators with immune checkpoint inhibitors in the surgical setting. Furthermore, we explore advances in multi-omics technologies that deepen our understanding of epigenetic-immune crosstalk. Ultimately, we emphasize targeting the epigenetic-immune axis as a strategy to enhance anti-tumor immunity and improve patient outcomes.
