伤害性神经支配限制三级淋巴结构促进肺癌
伤害性神经支配限制三级淋巴结构促进肺癌
作者： 小柯机器人 发布时间：2026/5/20 15:41:45
本期文章：《细胞》：Online/在线发表
伤害性神经支配限制三级淋巴结构促进肺癌，这一成果由弗朗西斯克里克研究所Leanne Li小组经过不懈努力而取得。2026年5月19日出版的《细胞》杂志发表了这项成果。
小组发现肺腺癌（LUAD）的进展局部放大了伤害感觉神经的支配和激活，从而驱动了一种主要感觉神经肽——降钙素基因相关肽（CGRP）的释放。CGRP作用于巨噬细胞的一个亚群，从而损害CXCL13 + 成纤维细胞的募集，并阻断三级淋巴样结构（TLS）的组装，这是LUAD预后的一个关键预测因子。局部感觉去神经支配恢复TLS形成，增强B和T细胞依赖性免疫，抑制肿瘤生长。香烟烟雾提取物（CSE）进一步激活这种神经回路，加速LUAD的进展。在暴露于CSE的动物中，药理学上的CGRP阻断使肿瘤对免疫治疗增敏并延长生存期。总之，他们的发现揭示了连接伤害性神经元、TLS和LUAD的神经免疫轴，并确定了神经源性炎症是吸烟促进肺肿瘤发生的一种独立于体细胞突变的机制。
据悉，感觉神经支配调节肺的生理和病理，但其在肺癌中的作用尚不清楚。
附：英文原文
Title: Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer
Author: Ya-Hsuan Ho, Giacomo Bregni, Marco Stazi, Paola Peinado, Pei-Hsing Chen, Claudio Ballabio, Victoire Boulat, Shree Vadera, Yilin Guan, Zhikai Liu, Alicia Alonso de la Vega, Li Wang, Chao-Chi Ho, Henrique Veiga-Fernandes, Julian Downward, Min-Shu Hsieh, Maksym V. Kopanitsa, George Kassiotis, Christoforos Tsantoulas, Michael S. Schappe, Michael-Bogdan Margineanu, Dinis Pedro Calado, Isaac M. Chiu, Charles Swanton, Jin-Shing Chen, Leanne Li
Issue&Volume: 2026-05-19
Abstract: Sensory innervation regulates lung physiology and pathology, but its role in lung cancer is poorly understood. We show that lung adenocarcinoma (LUAD) progression locally amplifies nociceptive sensory innervation and activation, which drives the release of a major sensory neuropeptide, calcitonin gene-related peptide (CGRP). CGRP acts on a subset of macrophages, thereby impairing the recruitment of CXCL13+ fibroblasts and blocking tertiary lymphoid structure (TLS) assembly, a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation, enhances B and T cell-dependent immunity, and suppresses tumor growth. Cigarette smoke extract (CSE) further activates this neural circuit to accelerate LUAD progression. In CSE-exposed animals, pharmacologic CGRP blockade sensitizes tumors to immunotherapy and prolongs survival. Together, our findings uncover a neuroimmune axis linking nociceptive neurons, TLS, and LUAD and identify neurogenic inflammation as a mechanism by which smoking promotes lung tumorigenesis independent of somatic mutagenesis.
DOI: 10.1016/j.cell.2026.04.038
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00505-2
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