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.

癌症相关成纤维细胞 (CAF) 是高度异质的。由于缺乏对 CAF 功能区别的全面了解，目前尚不清楚如何基于患者肿瘤中的 CAF 进行个性化癌症治疗。我们已经建立了一个来自患者非小细胞肺癌 (NSCLC) 活检的 CAF 活生物库，其中包含临床 NSCLC 中 CAF 的广泛分子谱。通过使用患者接受的相同疗法在功能上询问 CAF 异质性，我们确定了三种功能亚型：(1) 对癌症具有强大的保护作用，并高度表达 HGF 和 FGF7；(2)中度保护癌症，高表达FGF7；(3) 那些提供最低限度保护的人。CAFs 之间的这些功能差异是由它们内在的 TGF-β 信号控制的，抑制 HGF 和 FGF7 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，因此提供了指导个性化治疗的途径。