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Lang G, Mu DG, Yan S, Jiao Y, Wang HL. Neutrophil extracellular traps in gastrointestinal malignancies: Friend or foe? World J Gastrointest Oncol 2026; 18(12): 124869 [DOI: 10.4251/wjgo.124869]
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 124869 Published online Dec 15, 2026. doi: 10.4251/wjgo.124869
Neutrophil extracellular traps in gastrointestinal malignancies: Friend or foe?
Guang Lang, De-Gong Mu, Shuai Yan, Yan Jiao, He-Lei Wang
Guang Lang, De-Gong Mu, Shuai Yan, Department of the Third Operation Room, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Yan Jiao, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
He-Lei Wang, Department of Gastrointestinal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Co-first authors: Guang Lang and De-Gong Mu.
Co-corresponding authors: Yan Jiao and He-Lei Wang.
Author contributions: Lang G and Mu DG contributed to manuscript drafting and revision, and contributed equally as co-first authors; Yan S assisted with literature screening and table preparation; Jiao Y and Wang HL conceived the review, supervised the manuscript, and revised the intellectual content; Jiao Y and Wang HL contributed equally as co-corresponding authors. All authors read and approved the final manuscript.
AI contribution statement: ChatGPT was used only for English language editing and grammar refinement. The authors are solely responsible for the scientific content, interpretation, and conclusions presented in this manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: He-Lei Wang, Department of Gastrointestinal Surgery, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130021, Jilin Province, China. helei@jlu.edu.cn
Received: June 26, 2026 Revised: August 4, 2026 Accepted: September 24, 2026 Published online: December 15, 2026 Processing time: 137 Days and 11 Hours
Abstract
Neutrophil extracellular traps (NETs), chromatin-based webs released by activated neutrophils, were first described as antimicrobial scaffolds, but these structures now appear in sterile inflammation, thrombosis, and cancer. In gastrointestinal malignancies, experimental and clinical studies have connected NETs with tumor growth, immune escape, cancer-associated thrombosis, postoperative recurrence, and metastatic spread. NET-derived DNA, histones, neutrophil elastase, myeloperoxidase, and citrullinated histones can remodel the tumor microenvironment, shield tumor cells from cytotoxic lymphocytes, promote epithelial-mesenchymal transition, awaken dormant cells, and help metastatic cells colonize distant organs. However, NETs are not simply harmful. They remain part of host defense and may restrain tumor cells in selected inflammatory, infectious, or treatment-related settings. This review summarizes NET biology in colorectal, gastric, hepatocellular, pancreatic, and other gastrointestinal cancers, focusing on the therapies that inhibit NET formation, degrade NET scaffolds, or block NET-tumor cell interactions.
Core Tip: Neutrophil extracellular traps (NETs) are more than inflammatory debris in gastrointestinal cancer. Current evidence links these alterations to immune escape, thrombosis, metastatic niche formation, and treatment resistance. Their biology remains context-dependent because the same neutrophil program also protects against infection. Consequently, NET-targeted therapy should suppress pathogenic NET activity without broadly disabling neutrophil defenses.
