Mezawa Yoshihiro, Orimo Akira
Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
FEBS J. 2022 May;289(9):2429-2447. doi: 10.1111/febs.15851. Epub 2021 Apr 12.
Reciprocal interactions between cancer cells and stromal cells in the tumor microenvironment (TME) are essential for full-blown tumor development. Carcinoma-associated fibroblasts (CAFs) are a key component of the TME together with a wide variety of stromal cell types including vascular, inflammatory, and immune cells in the extracellular matrix. CAFs not only promote tumor growth, invasion, and metastasis, but also dampen the efficacy of various therapies including immune checkpoint inhibitors. CAFs are composed of distinct fibroblast populations presumably with diverse activated fibroblastic states and tumor-promoting phenotypes in a tumor, indicating intratumor heterogeneity in these fibroblasts. Given that CAFs have been implicated in both disease progression and therapeutic responses, elucidating the functional roles of each fibroblast population in CAFs and the molecular mechanisms mediating their phenotypic stability and plasticity in the TME would be crucial for understanding tumor biology. We herein discuss how distinct fibroblast populations comprising CAFs establish their cell identities, in terms of cells-of-origin, stimuli from the TME, and the phenotypes characteristic of activated states.
肿瘤微环境（TME）中癌细胞与基质细胞之间的相互作用对于肿瘤的全面发展至关重要。癌相关成纤维细胞（CAF）是TME的关键组成部分，与细胞外基质中的多种基质细胞类型（包括血管、炎症和免疫细胞）一起。CAF不仅促进肿瘤生长、侵袭和转移，还会削弱包括免疫检查点抑制剂在内的各种疗法的疗效。CAF由不同的成纤维细胞群体组成，这些群体可能在肿瘤中具有不同的活化成纤维细胞状态和促肿瘤表型，表明这些成纤维细胞存在肿瘤内异质性。鉴于CAF与疾病进展和治疗反应均有关联，阐明CAF中每个成纤维细胞群体的功能作用以及介导其在TME中表型稳定性和可塑性的分子机制对于理解肿瘤生物学至关重要。我们在此讨论构成CAF的不同成纤维细胞群体如何根据起源细胞、来自TME的刺激以及活化状态的特征表型来确定其细胞身份。
