Tumor Immunology and Immunotherapy Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Rome, Italy.
J Exp Clin Cancer Res. 2023 Dec 20;42(1):347. doi: 10.1186/s13046-023-02934-4.
In recent years, research focused on the multifaceted landscape and functions of cancer-associated fibroblasts (CAFs) aimed to reveal their heterogeneity and identify commonalities across diverse tumors for more effective therapeutic targeting of pro-tumoral stromal microenvironment. However, a unified functional categorization of CAF subsets remains elusive, posing challenges for the development of targeted CAF therapies in clinical settings.The CAF phenotype arises from a complex interplay of signals within the tumor microenvironment, where transcription factors serve as central mediators of various cellular pathways. Recent advances in single-cell RNA sequencing technology have emphasized the role of transcription factors in the conversion of normal fibroblasts to distinct CAF subtypes across various cancer types.This review provides a comprehensive overview of the specific roles of transcription factor networks in shaping CAF heterogeneity, plasticity, and functionality. Beginning with their influence on fibroblast homeostasis and reprogramming during wound healing and fibrosis, it delves into the emerging insights into transcription factor regulatory networks. Understanding these mechanisms not only enables a more precise characterization of CAF subsets but also sheds light on the early regulatory processes governing CAF heterogeneity and functionality. Ultimately, this knowledge may unveil novel therapeutic targets for cancer treatment, addressing the existing challenges of stromal-targeted therapies.
近年来，研究集中在癌症相关成纤维细胞 (CAFs) 的多方面景观和功能上，旨在揭示其异质性，并在不同肿瘤中识别共性，以更有效地靶向肿瘤基质微环境。然而，CAF 亚群的统一功能分类仍然难以捉摸，这对临床环境中靶向 CAF 治疗的发展提出了挑战。CAF 表型是肿瘤微环境中信号复杂相互作用的结果，转录因子作为各种细胞途径的中央介质。单细胞 RNA 测序技术的最新进展强调了转录因子在将正常成纤维细胞转化为不同 CAF 亚型中的作用，跨越各种癌症类型。本综述全面概述了转录因子网络在塑造 CAF 异质性、可塑性和功能中的特定作用。从它们在伤口愈合和纤维化过程中对成纤维细胞稳态和重编程的影响开始，深入探讨了转录因子调控网络的新见解。了解这些机制不仅能够更精确地表征 CAF 亚群，还揭示了早期调控 CAF 异质性和功能的过程。最终，这些知识可能揭示出癌症治疗的新的治疗靶点，解决基质靶向治疗的现有挑战。
