Pang JY, Jin RY, Zhang HX, Zhang YH, Wei XY, Cao WB, Chen YX, Wang JL, Mo SJ. Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies. World J Clin Oncol 2026; 17(2): 113674 [DOI: 10.5306/wjco.v17.i2.113674]
Corresponding Author of This Article
Sai-Jun Mo, Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Science Avenue, Zhongyuan District, Zhengzhou 450001, Henan Province, China. sjmo@zzu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Feb 24, 2026 (publication date) through Feb 12, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Oncology
ISSN
2218-4333
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Pang JY, Jin RY, Zhang HX, Zhang YH, Wei XY, Cao WB, Chen YX, Wang JL, Mo SJ. Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies. World J Clin Oncol 2026; 17(2): 113674 [DOI: 10.5306/wjco.v17.i2.113674]
Jia-Yu Pang, Rong-Yao Jin, Han-Xiao Zhang, Ying-Hua Zhang, Xin-Yue Wei, Wen-Bo Cao, Yi-Xiao Chen, Sai-Jun Mo, Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Jia-Yu Pang, The First Clinical College of Zhengzhou University, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Jun-Ling Wang, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Co-first authors: Jia-Yu Pang and Rong-Yao Jin.
Author contributions: Pang JY and Jin RY contributed to the work equally and are co-first authors of this manuscript; Pang JY and Jin RY wrote the draft; Zhang HX, Zhang YH, Wei XY, Cao WB, Chen YX, and Wang JL searched and collated the literature; Mo SJ designed and revised the manuscript; and all authors have read and approved the final manuscript.
Supported by the Foundation of Henan Educational Committee, No. 26A310017; the College Student Innovation and Entrepreneurship Competitions, No. S202510459221 and No. 2025cxcy639; the Natural Science Foundation of Henan, No. 242300421493; and the Medical Science and Technology Planning Project of Henan Province, No. LHGJ20220525.
Conflict-of-interest statement: Dr. Mo has a patent the Foundation of Henan Educational Committee (No. 26A310017) issued, a patent College Student Innovation and Entrepreneurship Competitions (No. 202510459174 and No. 2025cxcy639) issued; and Wang JL has a patent Natural Science Foundation of Henan (No. 242300431493) issued, and a patent the Medical Science and Technology Planning Project of Henan Province (No. LHGJ20220525) issued.
Corresponding author: Sai-Jun Mo, Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, No. 100 Science Avenue, Zhongyuan District, Zhengzhou 450001, Henan Province, China. sjmo@zzu.edu.cn
Received: September 2, 2025 Revised: October 24, 2025 Accepted: December 19, 2025 Published online: February 24, 2026 Processing time: 158 Days and 23.9 Hours
Abstract
Digestive tract tumors represent a substantial global public health challenge, accounting for elevated morbidity and mortality rates. Perineural invasion (PNI), the spread of tumor cells along nerve fibers, has emerged as a key driver of aggressiveness and a poor prognosis. This study systematically reviews the complex, underexplored interplay between PNI and antitumor immunity in gastrointestinal cancers. By analyzing immune-related components (the programmed cell death protein 1/programmed death ligand 1 axis, T cell subsets, tumor-associated macrophages, and other immune checkpoints), it reveals PNI disrupts immune balance: It suppresses T-cell activity via programmed death ligand 1/programmed cell death protein 1 binding, skews T-cell differentiation to reduce antitumor efficacy and boost immunosuppression, and polarizes macrophages to aid tumor progression. These findings provide novel insights into how PNI reshapes the tumor immune microenvironment and promotes metastatic behavior, establishing a framework for prioritizing immunotherapeutic targets to inform precision treatment strategies.
Core Tip: Digestive tract tumors remain a major global health burden with high morbidity and mortality. Perineural invasion (PNI), the infiltration of tumor cells along nerves, is a key determinant of tumor aggressiveness and poor outcome. This review systematically investigates the crosstalk between PNI and immune mechanisms in gastrointestinal cancers, with a focus on critical components, including the programmed cell ligand 1/programmed cell 1 axis, T cells, macrophages, and other immune checkpoints. It reveals mechanisms by which PNI reshapes the tumor immune microenvironment to promote metastasis, identify candidate immunotherapeutic targets, and provide a foundation for developing precision treatment strategies.
