天津医科大学肿瘤研究所郝继辉课题组在研究中取得进展。他们的最新研究揭示了痛觉感受器神经元通过与癌症相关成纤维细胞和抑制自然杀伤细胞的相互作用促进PDAC的进展和癌症疼痛。这一研究成果发表在2025年3月24日出版的国际学术期刊《细胞研究》上。

该课题组人员进一步证明，在PDAC的肿瘤微环境中，伤害受体神经元通过降钙素基因相关肽（CGRP）和神经生长因子（NGF）与癌症相关成纤维细胞（CAFs）相互作用。这种相互作用抑制CAFs中白细胞介素-15的表达，抑制了自然杀伤（NK）细胞的浸润和细胞毒功能，从而促进了PDAC的进展和癌性疼痛。在PDAC患者中，肿瘤组织的伤害性神经支配与NK细胞浸润呈负相关，与疼痛强度呈正相关。这种关联是PDAC患者总生存期和无复发生存期的独立预后因素。他们的发现强调了在PDAC的发展过程中，伤害感受器神经元通过与CAFs的相互作用对NK细胞的重要调节。该研究团队还提出，靶向伤害感受器神经元或CGRP信号可能为PDAC和癌性疼痛提供有希望的治疗方法。

据悉，癌症神经科学这一新兴领域在揭示神经系统在癌症发生和发展中的关键作用方面取得了巨大进展。胰腺导管腺癌（PDAC）以神经周围浸润为特征，受自主神经（交感神经和副交感神经）和感觉神经支配。

附：英文原文

Title: Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells

Author: Wang, Kaiyuan, Ni, Bo, Xie, Yongjie, Li, Zekun, Yuan, Limei, Meng, Chenyang, Zhao, Tiansuo, Gao, Song, Huang, Chongbiao, Wang, Hongwei, Ma, Ying, Zhou, Tianxing, Feng, Yukuan, Chang, Antao, Yang, Chao, Yu, Jun, Yu, Wenwen, Zang, Fenglin, Zhang, Yanhui, Ji, Ru-Rong, Wang, Xiuchao, Hao, Jihui

Issue&Volume: 2025-03-24

Abstract: The emerging field of cancer neuroscience has demonstrated great progress in revealing the crucial role of the nervous system in cancer initiation and progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized by perineural invasion and modulated by autonomic (sympathetic and parasympathetic) and sensory innervations. Here, we further demonstrated that within the tumor microenvironment of PDAC, nociceptor neurons interacted with cancer-associated fibroblasts (CAFs) through calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF). This interaction led to the inhibition of interleukin-15 expression in CAFs, suppressing the infiltration and cytotoxic function of natural killer (NK) cells and thereby promoting PDAC progression and cancer pain. In PDAC patients, nociceptive innervation of tumor tissue is negatively correlated with the infiltration of NK cells while positively correlated with pain intensity. This association serves as an independent prognostic factor for both overall survival and relapse-free survival for PDAC patients. Our findings highlight the crucial regulation of NK cells by nociceptor neurons through interaction with CAFs in the development of PDAC. We also propose that targeting nociceptor neurons or CGRP signaling may offer a promising therapy for PDAC and cancer pain.

DOI: 10.1038/s41422-025-01098-4

Source: https://www.nature.com/articles/s41422-025-01098-4