Transforming growth factor-β (TGFβ) signalling controls multiple cell fate decisions during development and tissue homeostasis; hence, dysregulation of this pathway can drive several diseases, including cancer. Here we discuss the influence that TGFβ exerts on the composition and behaviour of different cell populations present in the tumour immune microenvironment, and the context-dependent functions of this cytokine in suppressing or promoting cancer. During homeostasis, TGFβ controls inflammatory responses triggered by exposure to the outside milieu in barrier tissues. Lack of TGFβ exacerbates inflammation, leading to tissue damage and cellular transformation. In contrast, as tumours progress, they leverage TGFβ to drive an unrestrained wound-healing programme in cancer-associated fibroblasts, as well as to suppress the adaptive immune system and the innate immune system. In consonance with this key role in reprogramming the tumour microenvironment, emerging data demonstrate that TGFβ-inhibitory therapies can restore cancer immunity. Indeed, this approach can synergize with other immunotherapies — including immune checkpoint blockade — to unleash robust antitumour immune responses in preclinical cancer models. Despite initial challenges in clinical translation, these findings have sparked the development of multiple therapeutic strategies that inhibit the TGFβ pathway, many of which are currently in clinical evaluation.

转化生长因子-β (TGFβ) 信号控制发育和组织稳态期间的多个细胞命运决定；因此，该通路的失调会导致多种疾病，包括癌症。在这里，我们讨论了 TGFβ 对肿瘤免疫微环境中存在的不同细胞群的组成和行为的影响，以及这种细胞因子在抑制或促进癌症方面的依赖性功能。在体内平衡期间，TGFβ 控制屏障组织中因暴露于外部环境而引发的炎症反应。缺乏 TGFβ 会加剧炎症，导致组织损伤和细胞转化。相反，随着肿瘤的进展，它们利用 TGFβ 来驱动癌症相关成纤维细胞中不受限制的伤口愈合程序，以及抑制适应性免疫系统和先天免疫系统。与这一在重编程肿瘤微环境中的关键作用一致，新出现的数据表明 TGFβ 抑制疗法可以恢复癌症免疫力。事实上，这种方法可以与其他免疫疗法（包括免疫检查点阻断）协同作用，在临床前癌症模型中释放出强大的抗肿瘤免疫反应。尽管在临床转化方面存在最初的挑战，但这些发现已经激发了抑制 TGFβ 通路的多种治疗策略的发展，其中许多目前正在临床评估中。这种方法可以与其他免疫疗法（包括免疫检查点阻断）协同作用，在临床前癌症模型中释放出强大的抗肿瘤免疫反应。尽管在临床转化方面存在最初的挑战，但这些发现已经激发了抑制 TGFβ 通路的多种治疗策略的发展，其中许多目前正在临床评估中。这种方法可以与其他免疫疗法（包括免疫检查点阻断）协同作用，在临床前癌症模型中释放出强大的抗肿瘤免疫反应。尽管在临床转化方面存在最初的挑战，但这些发现已经激发了抑制 TGFβ 通路的多种治疗策略的发展，其中许多目前正在临床评估中。