文章：

克服肿瘤中TGFβ介导的免疫逃避

Overcoming TGFβ-mediated immune evasion in cancer

原文发布日期：2021-10-20

DOI: 10.1038/s41568-021-00413-6

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

转化生长因子-β（TGFβ）信号通路在发育和组织稳态过程中调控多种细胞命运决定，因此该通路的失调可驱动包括癌症在内的多种疾病。本文探讨TGFβ对肿瘤免疫微环境中不同细胞群体的组成和行为所产生的影响，以及该细胞因子在抑制或促进癌症方面的环境依赖性功能。在稳态状态下，TGFβ控制屏障组织因暴露于外界环境而触发的炎症反应。TGFβ的缺失会加剧炎症，导致组织损伤和细胞转化。相反，在肿瘤进展过程中，癌细胞利用TGFβ驱动癌症相关成纤维细胞进行无节制的伤口愈合程序，并抑制适应性免疫系统和先天免疫系统。与TGFβ在重编程肿瘤微环境中的这一关键作用相一致，新出现的数据表明，TGFβ抑制疗法可以恢复癌症免疫力。实际上，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强大的抗肿瘤免疫反应。尽管在临床转化方面面临初步挑战，这些发现已推动多种抑制TGFβ通路治疗策略的发展，其中许多目前正处于临床评估阶段。

原文链接：

Overcoming TGFβ-mediated immune evasion in cancer