Cancer-associated fibroblasts (CAFs) found in primary and metastatic tumours are highly versatile, plastic and resilient cells that are actively involved in cancer progression through complex interactions with other cell types in the tumour microenvironment. As well as generating extracellular matrix components that contribute to the structure and function of the tumour stroma, CAFs undergo epigenetic changes to produce secreted factors, exosomes and metabolites that influence tumour angiogenesis, immunology and metabolism. Because of their putative pro-oncogenic functions, CAFs have long been considered an attractive therapeutic target; however, clinical trials of treatment strategies targeting CAFs have mostly ended in failure and, in some cases, accelerated cancer progression and resulted in inferior survival outcomes. Importantly, CAFs are heterogeneous cells and their characteristics and interactions with other cell types might change dynamically as cancers evolve. Studies involving single-cell RNA sequencing and novel mouse models have increased our understanding of CAF diversity, although the context-dependent roles of different CAF populations and their interchangeable plasticity remain largely unknown. Comprehensive characterization of the tumour-promoting and tumour-restraining activities of CAF subtypes, including how these complex bimodal functions evolve and are subjugated by neoplastic cells during cancer progression, might facilitate the development of novel diagnostic and therapeutic approaches. In this Review, the clinical relevance of CAFs is summarized with an emphasis on their value as prognosis factors and therapeutic targets.

在原发性和转移性肿瘤中发现的癌症相关成纤维细胞 (CAF) 是高度通用、可塑性和有弹性的细胞，它们通过与肿瘤微环境中其他细胞类型的复杂相互作用积极参与癌症进展。除了产生有助于肿瘤基质结构和功能的细胞外基质成分外，CAF 还经历表观遗传变化以产生影响肿瘤血管生成、免疫学和代谢的分泌因子、外泌体和代谢物。由于其推定的促癌功能，CAFs 长期以来一直被认为是一个有吸引力的治疗靶点。然而，针对 CAF 的治疗策略的临床试验大多以失败告终，在某些情况下，会加速癌症进展并导致较差的生存结果。重要的，CAF 是异质细胞，它们的特征和与其他细胞类型的相互作用可能随着癌症的发展而动态变化。涉及单细胞 RNA 测序和新型小鼠模型的研究增加了我们对 CAF 多样性的理解，尽管不同 CAF 种群的上下文相关作用及其可互换的可塑性在很大程度上仍然未知。对 CAF 亚型的肿瘤促进和肿瘤抑制活性的全面表征，包括这些复杂的双峰功能在癌症进展过程中如何演变和被肿瘤细胞抑制，可能有助于开发新的诊断和治疗方法。在这篇综述中，总结了 CAF 的临床相关性，并强调了它们作为预后因素和治疗靶点的价值。