Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Front Immunol. 2022 Dec 19;13:1061394. doi: 10.3389/fimmu.2022.1061394. eCollection 2022.
Transforming growth factor-β (TGF-β) signaling regulates multiple physiological processes, such as cell proliferation, differentiation, immune homeostasis, and wound healing. Besides, TGF-β plays a vital role in diseases, including cancer. Accumulating evidence indicates that TGF-β controls the composition and behavior of immune components in the tumor microenvironment (TME). Advanced cancers leverage TGF-β to reshape the TME and escape immune surveillance. TGF-β-mediated immune evasion is an unfavorable factor for cancer immunotherapy, especially immune checkpoint inhibitors (ICI). Numerous preclinical and clinical studies have demonstrated that hyperactive TGF-β signaling is closely associated with ICI resistance. It has been validated that TGF-β blockade synergizes with ICI and overcomes treatment resistance. TGF-β-targeted therapies, including trap and bispecific antibodies, have shown immense potential for cancer immunotherapy. In this review, we summarized the predictive value of TGF-β signaling and the prospects of TGF-β-targeted therapies for cancer immunotherapy.
转化生长因子-β（TGF-β）信号通路调节多种生理过程，如细胞增殖、分化、免疫稳态和伤口愈合。此外，TGF-β在包括癌症在内的多种疾病中发挥重要作用。越来越多的证据表明，TGF-β控制肿瘤微环境（TME）中免疫成分的组成和行为。晚期癌症利用 TGF-β重塑 TME 并逃避免疫监视。TGF-β介导的免疫逃逸是癌症免疫治疗，特别是免疫检查点抑制剂（ICI）的不利因素。大量的临床前和临床研究表明，过度活跃的 TGF-β信号与 ICI 耐药密切相关。已经证实 TGF-β阻断与 ICI 协同作用并克服治疗耐药性。TGF-β靶向疗法，包括陷阱和双特异性抗体，在癌症免疫治疗方面显示出巨大的潜力。在这篇综述中，我们总结了 TGF-β信号的预测价值以及 TGF-β靶向疗法在癌症免疫治疗中的前景。
