Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Institute for Intelligent Bio/Chem Manufacturing (iBCM), Zhejiang University (ZJU)-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China.
Front Immunol. 2022 May 26;13:891268. doi: 10.3389/fimmu.2022.891268. eCollection 2022.
Since TGF-β was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-β in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-β is the principal regulator of the immune system, as deprivation of TGF-β signaling completely abrogates adaptive immunity. However, enhancing TGF-β signaling constrains the immune response through multiple mechanisms, including boosting Treg cell differentiation and inducing CD8 T-cell apoptosis in the disease context. The love-hate relationship between TGF-β signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-β, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-β inhibition and immunotherapy have provide insights into the development of TGF-β-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-β and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-β signaling pathways as an emerging area of cancer therapy.
自十年前 TGF-β 被认为是胚胎发生和成人组织稳态中必不可少的分泌细胞因子以来，我们对 TGF-β 在哺乳动物发育和疾病（特别是癌症）中的作用的了解一直在不断更新。越来越多的证据证实，TGF-β 是免疫系统的主要调节剂，因为剥夺 TGF-β 信号完全消除了适应性免疫。然而，通过多种机制增强 TGF-β 信号会抑制免疫反应，包括促进 Treg 细胞分化并在疾病情况下诱导 CD8 T 细胞凋亡。TGF-β 信号与免疫系统之间的爱恨关系使得开发针对 TGF-β 的有效单药疗法具有挑战性，特别是用于癌症治疗。尽管如此，最近关于 TGF-β 抑制和免疫疗法联合治疗的研究为开发 TGF-β 靶向疗法提供了新的思路，并在晚期癌症患者中取得了良好的效果。因此，我们总结了 TGF-β 与免疫系统在发育和肿瘤背景下的纠缠，并探讨了劫持关键 TGF-β 信号通路作为癌症治疗新领域的最新进展。
