宾夕法尼亚大学金橙橙课题组宣布他们的最新研究提出了肿瘤-脑串扰通过感觉-交感轴抑制癌症免疫。2026年2月4日出版的《自然》杂志发表了这项成果。

在这里，课题组研究人员确定了肿瘤-脑轴，通过建立免疫抑制肿瘤微环境促进肿瘤发生。结合基因工程小鼠模型、神经示踪、组织成像和单细胞转录组学，课题组证明肺腺癌诱导迷走神经感觉神经元的神经支配和功能参与，迷走神经感觉神经元是连接内脏器官和大脑的主要内感受系统。

从机制上讲，表达Npy2r的迷走感觉神经将信号从肺肿瘤传递到脑干核，在肿瘤微环境中驱动交感传出活动的升高。这反过来又通过肺泡巨噬细胞中的β2肾上腺素能信号抑制抗肿瘤免疫。通过遗传、药理学或化学发生途径破坏这种感觉-交感通路，通过增强对癌症的免疫反应，显著抑制肺癌的生长。

总的来说，这些结果揭示了肿瘤与大脑的双向交流，包括迷走神经感觉输入和交感神经输出，共同调节抗癌免疫；靶向这种肿瘤-脑回路可能为内脏器官癌症提供新的治疗方法。

据悉，体脑通讯已成为组织稳态的关键调节因子。实体瘤受周围神经系统不同分支的支配，肿瘤神经支配的增加与癌症预后不良有关。然而，目前尚不清楚大脑如何感知和响应外周器官的肿瘤，以及肿瘤与大脑的交流如何影响癌症免疫。

附：英文原文

Title: Tumour–brain crosstalk restrains cancer immunity via a sensory–sympathetic axis

Author: Wei, Haohan K., Yu, Chuyue D., Hu, Bo, Zeng, Xing, Ichise, Hiroshi, Li, Liang, Wang, Yu, Wang, Ruiqi L., Germain, Ronald N., Chang, Rui B., Jin, Chengcheng

Issue&Volume: 2026-02-04

Abstract: Body–brain communication has emerged as a key regulator of tissue homeostasis1,2,3,4,5. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes6,7,8. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity. Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain. Mechanistically, Npy2r-expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β2 adrenergic signalling in alveolar macrophages. Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer. Collectively, these results reveal a bidirectional tumour–brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour–brain circuit may provide new treatments for visceral organ cancers.

DOI: 10.1038/s41586-025-10028-8

Source: https://www.nature.com/articles/s41586-025-10028-8