Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.
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DOI：
10.1016/j.ccell.2017.02.008
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发表时间：
2017-03-13
期刊：
影响因子：
50.3
通讯作者：
Greenberg PD
中科院分区：
文献类型：
--
作者：
Anderson KG;Stromnes IM;Greenberg PD
实体瘤中的 T 细胞功能障碍是由多种机制造成的。肿瘤细胞中信号通路的改变有助于产生富含抑制性细胞的抑制性肿瘤微环境，这对癌症免疫构成了主要障碍。对细胞功能和存活的代谢限制影响肿瘤进展和免疫细胞功能。面对持久性抗原，慢性 T 细胞受体信号传导驱动 T 淋巴细胞进入功能衰竭状态。在这里，我们讨论肿瘤及其微环境如何影响 T 细胞运输和功能，重点关注黑色素瘤、胰腺癌和卵巢癌，并讨论科学进步如何帮助克服这些障碍。
T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.