复旦大学江一舟小组的一项最新研究揭示了感觉神经元通过刺激乳腺癌肿瘤微环境中的致密细胞外基质来驱动免疫排斥。该项研究成果发表在2026年2月5日出版的《细胞》上。
该研究组发现TNBC生态系统中的主要神经元类型感觉神经元通过刺激致密的细胞外基质来驱动免疫排斥肿瘤微环境（TME）。机制上，TME中高浓度的神经生长因子（NGF）触发感觉神经元分泌神经肽降钙素基因相关肽（CGRP），从而激活癌症相关成纤维细胞（CAFs）分泌胶原。具体来说，CGRP与其受体RAMP1（受体活性修饰蛋白1）结合，激活环AMP (cAMP)/蛋白激酶A (PKA)/cAMP反应元件结合蛋白1 （CREB1）信号，增加胶原沉积。临床上，在TNBC中，靶向感觉神经元重塑紊乱的TME，并与抗程序性细胞死亡蛋白1 （PD-1）免疫治疗协同。总的来说，他们的发现揭示了感觉神经元和阻碍TNBC抗肿瘤免疫的CAF之间的联系。CGRP拮抗剂rimegetant具有临床转化潜力，可作为增强肿瘤免疫治疗的免疫增敏剂。
据悉，神经支配在肿瘤进展中起关键作用。然而，感觉神经元在三阴性乳腺癌（TNBC）生态系统中的作用仍不清楚。
附：英文原文
Title: Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment
Author: Si-Wei Zhang, Han Wang, Yi Xiao, Luo-Tian Liu, Minhong Shen, Zhuang Wang, Shen Zhao, Xiao-Hong Ding, Ying Wang, Qing-Yuan Zhuang, Jinfei Ni, Zhi-Ming Shao, Yi-Zhou Jiang
Issue&Volume: 2026-02-05
Abstract: Innervation is critical in tumor progression. However, the involvement of sensory neurons in the ecosystem of triple-negative breast cancer (TNBC) remains poorly elucidated. Here, we decipher that sensory neurons, the dominant neuron type in the TNBC ecosystem, drive the immune-excluded tumor microenvironment (TME) by stimulating a dense extracellular matrix. Mechanistically, a high concentration of nerve growth factor (NGF) in TME triggers sensory neurons to secrete the neuropeptide calcitonin gene-related peptide (CGRP), thereby activating cancer-associated fibroblasts (CAFs) to secrete collagen. Specifically, CGRP binds to its receptor RAMP1 (receptor activity modifying protein 1), which is expressed mainly on CAFs, and subsequently activates cyclic AMP (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein 1 (CREB1) signaling to increase collagen deposition. Clinically, targeting sensory neurons remodels the disordered TME and synergizes with anti-programmed cell death protein 1 (PD-1) immunotherapy in TNBC. Collectively, our findings reveal a connection between sensory neurons and CAFs that obstructs antitumor immunity in TNBC. The CGRP antagonist rimegepant thus has clinical translational potential as an immuno-sensitizer to augment tumor immunotherapy.
DOI: 10.1016/j.cell.2026.01.001
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00048-6