©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Feb 24, 2026; 17(2): 113674
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.113674
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.113674
Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies
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
Revised: October 24, 2025
Accepted: December 19, 2025
Published online: February 24, 2026
Processing time: 158 Days and 23.9 Hours
Core Tip
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.