美国哈佛大学医学院、马萨诸塞州总医院的胡海川（Haichuan Hu）等研究人员合作发现，肺癌成纤维细胞的三种亚型确定了不同的治疗范式。2021年10月7日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员建立了一个癌症相关成纤维细胞（CAF）活体生物库，这来自于患者的非小肺癌（NSCLC）的活体组织，包括了临床NSCLC中CAF的广泛分子谱。通过使用患者接受的相同治疗方法对CAF的异质性进行功能检测，研究人员确定了三种功能亚型。(1)对癌症有强有力的保护作用，并高度表达HGF和FGF7；(2)对癌症有中等程度的保护作用，并高度表达FGF7；(3)那些提供最低限度的保护。

CAF之间的这些功能差异受其固有的TGF-β信号支配，TGF-β信号抑制HGF和FGF7的表达。这种CAF功能分类与患者对靶向治疗的临床反应相关，也与肿瘤免疫微环境相关，因此提供了一个指导个性化治疗的途径。

据介绍，CAF是高度异质性的。由于缺乏对CAF功能区别的全面了解，目前仍不清楚如何根据患者肿瘤中的CAF进行个性化癌症治疗。

附：英文原文

Title: Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms

Author: Haichuan Hu, Zofia Piotrowska, Patricia J. Hare, Huidong Chen, Hillary E. Mulvey, Aislinn Mayfield, Sundus Noeen, Krystina Kattermann, Max Greenberg, August Williams, Amanda K. Riley, Jarad J. Wilson, Ying-Qing Mao, Ruo-Pan Huang, Mandeep K. Banwait, Jeffrey Ho, Giovanna S. Crowther, Lida P. Hariri, Rebecca S. Heist, David P. Kodack, Luca Pinello, Alice T. Shaw, Mari Mino-Kenudson, Aaron N. Hata, Lecia V. Sequist, Cyril H. Benes, Matthew J. Niederst, Jeffrey A. Engelman

Issue&Volume: 2021-10-07

Abstract: Cancer-associated fibroblasts (CAFs) are highly heterogeneous. With the lack of a comprehensive understanding of CAFs' functional distinctions, it remains unclear how cancer treatments could be personalized based on CAFs in a patient's tumor. We have established a living biobank of CAFs derived from biopsies of patients' non-small lung cancer (NSCLC) that encompasses a broad molecular spectrum of CAFs in clinical NSCLC. By functionally interrogating CAF heterogeneity using the same therapeutics received by patients, we identify three functional subtypes: (1) robustly protective of cancers and highly expressing HGF and FGF7; (2) moderately protective of cancers and highly expressing FGF7; and (3) those providing minimal protection. These functional differences among CAFs are governed by their intrinsic TGF-β signaling, which suppresses HGF and FGF7 expression. This CAF functional classification correlates with patients' clinical response to targeted therapies and also associates with the tumor immune microenvironment, therefore providing an avenue to guide personalized treatment.

DOI: 10.1016/j.ccell.2021.09.003

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00492-X