TGF-β对肿瘤微环境中免疫监视及细胞外基质的调控作用

Regulation of TGF-βon the Immune Surveillance and Extracellular Matrix of Tumor Microenvironment

转化生长因子β(transforming growth factorβ,TGF-β)是一种多功能的细胞因子,能够调控细胞增殖、分化、黏附、迁移及凋亡等行为,在胚胎发育过程和成体组织稳态维持中发挥重要的作用。而在许多疾病状态下,特别是在癌症中,TGF-β不仅能够影响肿瘤细胞的增殖与转移,其对于肿瘤微环境的调控与塑造也受到越来越多的关注。肿瘤微环境是指肿瘤在发生和发展过程中所处的内环境,由肿瘤细胞本身、相邻正常组织中的间质细胞,以及这些细胞所释放的众多细胞因子等共同组成。肿瘤微环境是肿瘤发展的重要机制,也是肿瘤临床治疗领域亟待探索的关键问题。TGF-β是调节肿瘤微环境组成和功能的主要参与者之一。在本综述中,将着重讨论TGF-β对于肿瘤微环境中的免疫监视机制及肿瘤细胞外基质的主要影响。即TGF-β对于构成先天性和获得性抗肿瘤免疫应答的各种类群的免疫细胞具有广泛的调控作用,从而削弱宿主的肿瘤免疫监视功能。同时,TGF-β通过促进肿瘤相关成纤维细胞的产生,以及肿瘤细胞外基质的纤维化,有助于肿瘤的恶变和转移。此外,还介绍了通过阻断肿瘤微环境中TGF-β信号通路进行肿瘤治疗的主要策略及独特优势。而未来进一步解析TGF-β信号在肿瘤微环境中的复杂调控作用,并建立有效的靶向干预方法对于开发高效的抗肿瘤药物具有重要的意义。

Transforming growth factorβ(TGF-β)is a multifunctional cytokine that can regulate cell proliferation,differentiation,adhesion,migration,apoptosis and other behaviors.It plays an important role in embryonic development and maintenance of adult tissue homeostasis.In many pathological states,especially in cancer,TGF-βnot only affects the proliferation and metastasis of tumor cells,but also functions as an important regulator in the tumor microenvironment.The tumor microenvironment refers to the internal environment of the tumor during its development,which is composed of tumor cells,stromal cells in adjacent normal tissues,and many cytokines released by these cells.The tumor microenvironment is important for tumor development,and also a key issue in tumor clinical treatment.TGF-β is one of the main participants in regulating the composition and function of tumor microenvironment.In this review,we focus on the main effects of TGF-β on the immune surveillance mechanism and extracellular matrix in the tumor microenvironment.TGF-βhas a wide range of regulatory effects on various linages of immune cells constituting innate and acquired anti-tumor immune responses,thereby weakening the host’s tumor immune surveillance function.Meanwhile,TGF-β promotes the production of tumor-associated fibroblasts and the fibrosis of the extracellular matrix of tumors,which helps the malignancy and metastasis of tumors.In addition,we introduce the main strategies and unique advantages of tumor treatment by blocking the TGF-β signaling pathway in the tumor microenvironment.Further analysis of the complex regulatory role of TGF-β signaling in the tumor microenvironment and the establishment of effective targeted therapy are of great significance for the development of highly effective anti-tumor drugs.