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World J Clin Oncol. Jun 24, 2026; 17(6): 121085
Published online Jun 24, 2026. doi: 10.5306/wjco.121085
Published online Jun 24, 2026. doi: 10.5306/wjco.121085
Prominent crosstalks between perineural invasion and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma
Shuai Sun, Rong-Jing Zhou, Ting-Ting Zhang, Jun-Jun Du, Hai-Fei Zhao, Department of Pathology, Hangzhou Cancer Hospital, Hangzhou 310002, Zhejiang Province, China
Si-Lin Xiang, Department of Graduate, Zhejiang Chinese Medical University, Hangzhou 310002, Zhejiang Province, China
Yan-Zhen Xu, Xiang-Yun He, Zhi-Bo Zuo, Department of Pathology, Westlake University Affiliated Hangzhou First People’s Hospital, Hangzhou 310002, Zhejiang Province, China
Xin Pan, Department of Pathology, Chun’an County First People’s Hospital, Hangzhou 310002, Zhejiang Province, China
Co-corresponding authors: Shuai Sun and Rong-Jing Zhou.
Author contributions: Sun S and Zhou RJ conceptualized and designed the study as co-corresponding authors; Sun S and Xiang SL performed the literature search and drafted the original manuscript; Zhang TT, Du JJ, Zhao HF, Xu YZ, Pan X, He XY, and Zuo ZB collected the data and assisted in figure preparation; Sun S, Zhou RJ, and Xiang SL critically revised the manuscript for important intellectual content; all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Shuai Sun, Department of Pathology, Hangzhou Cancer Hospital, No. 34 Yanguan Lane, Shangcheng District, Hangzhou 310002, Zhejiang Province, China.
Received: March 16, 2026
Revised: April 28, 2026
Accepted: June 4, 2026
Published online: June 24, 2026
Processing time: 99 Days and 3 Hours
Revised: April 28, 2026
Accepted: June 4, 2026
Published online: June 24, 2026
Processing time: 99 Days and 3 Hours
Core Tip
Core Tip: Perineural invasion is a bidirectional program in pancreatic ductal adenocarcinoma. It is sustained by crosstalks between tumor cells, nerves, and the immunosuppressive tumor microenvironment. The cellular compartments in tumor microenvironment collectively establish an immunosuppressive perineural niche. This niche enables neural dissemination, chemotherapy resistance, and cancer-associated pain. Adrenergic and cholinergic signaling amplifies this immunosuppression. Schwann cells actively guide tumor migration along nerve trunks. Therapeutic strategies targeting the neural-immune axis hold transformative potential for pancreatic ductal adenocarcinoma management.