TGFβ: Signaling Blockade for Cancer Immunotherapy.

TGFβ: Signaling Blockade for Cancer Immunotherapy.
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DOI:
10.1146/annurev-cancerbio-070620-103554
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发表时间:
2022
影响因子:
7.7
通讯作者:
Akhurst, Rosemary J.
Akhurst, Rosemary J.
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Szu-Ying;Mamai, Ons;Akhurst, Rosemary J.

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转化生长因子β (TGFβ)是一种有效的多效性细胞因子,对大多数细胞类型具有环境依赖性作用。它在某些癌症中作为肿瘤抑制因子和/或通过其对肿瘤基质和免疫微环境的影响支持肿瘤的进展和转移。在tgf β应答性肿瘤中,它可以通过上皮-间质转化、癌症干细胞特征的出现以及对许多药物类别(包括检查点阻断免疫疗法)的耐药性来促进侵袭和转移。在这里,我们考虑TGFβ作用于不同细胞的生物活性,与改善患者的免疫治疗结果相关,重点是适应性免疫系统。我们讨论了以肿瘤特异性或细胞类型特异性方式靶向TGFβ信号通路的药物开发的最新进展,以改善反应率和不良反应之间的治疗窗口。
Discovered over four decades ago, transforming growth factor β (TGFβ) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFβ-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal transformation, the appearance of cancer stem cell features, and resistance to many drug classes, including checkpoint blockade immunotherapies. Here we consider the biological activities of TGFβ action on different cells of relevance toward improving immunotherapy outcomes for patients, with a focus on the adaptive immune system. We discuss recent advances in the development of drugs that target the TGFβ signaling pathway in a tumor-specific or cell type–specific manner to improve the therapeutic window between response rates and adverse effects.
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