Division of Hematology, Mayo Clinic, Rochester, MN, United States.
Front Immunol. 2024 Nov 1;15:1451791. doi: 10.3389/fimmu.2024.1451791. eCollection 2024.
Recent breakthroughs in research have sparked a paradigm shift in our understanding of cancer biology, uncovering the critical role of the crosstalk between tumor cells and the immune cells of the tumor microenvironment (TME) in malignant transformation. Fibroblasts have long been viewed as ancillary participants in cancer progression, often eclipsed by the prominence given to malignant cells. Novel investigations, however, have increasingly acknowledged the essential part played by the fibroblasts and their phenotypic doppelganger cancer-associated fibroblasts (CAFs) in fostering immunosuppression and promoting tumor progression. Here we review the cell-of-origin from which CAFs derive and their altered programs compared to their normal counterpart. We will also discuss the complex interplay between CAFs and the surrounding immune cells of the TME in the context of solid tumors and B cell lymphomas, with a focus on the "reprogrammable" role of CAFs in immunosuppression, immuno-activation and immuno-avoidance, and their implications on drug resistance. Finally, we will examine the existing and plausible therapeutic approaches targeting CAFs as a strategy to enhance treatment response.
近年来的研究突破引发了我们对癌症生物学理解的范式转变，揭示了肿瘤细胞与肿瘤微环境（TME）中免疫细胞之间相互作用在恶性转化中的关键作用。成纤维细胞长期以来一直被视为癌症进展的辅助参与者，往往被恶性细胞的突出地位所掩盖。然而，新的研究越来越多地承认成纤维细胞及其表型类似物——癌相关成纤维细胞（CAFs）在促进免疫抑制和促进肿瘤进展方面所起的重要作用。在这里，我们回顾了 CAFs 的细胞起源及其与正常细胞相比的改变程序。我们还将讨论 CAFs 与实体瘤和 B 细胞淋巴瘤中 TME 周围免疫细胞之间的复杂相互作用，重点关注 CAFs 在免疫抑制、免疫激活和免疫逃避中的“可重编程”作用，以及它们对药物耐药性的影响。最后，我们将研究针对 CAFs 的现有和可行的治疗方法，作为增强治疗反应的一种策略。
