Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAF changes over time in breast cancer progression, with direct clinical implications.

肿瘤由癌症相关成纤维细胞（CAF）支持。 CAF 具有异质性，具有不同的癌症相关功能。了解 CAF 的全部功能及其随着肿瘤进化的动态变化可以提高癌症治疗的精度。在这里，我们使用索引和转录单细胞分选在小鼠乳腺肿瘤进展的几个时间点全面分析 CAF，揭示不同的亚群。值得注意的是，这些亚群的转录程序随着时间和转移而变化，从免疫调节程序转变为伤口愈合和抗原呈递程序，表明 CAF 及其功能是动态的。在人类乳腺肿瘤中也发现了两个主要的 CAF 亚群，它们的比例与各亚型的疾病结果相关，尤其与三阴性乳腺癌中的BRCA突变相关。这些发现表明，CAF 的全部成分在乳腺癌进展过程中随时间而变化，具有直接的临床意义。