Anderson Kristin G, Stromnes Ingunn M, Greenberg Philip D
Clinical Research Division, Fred Hutchinson Cancer Research Center, Mail Stop D3-100, P.O. Box 19024, Seattle, WA 98109, USA; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Departments of Medicine/Oncology and Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Mail Stop D3-100, P.O. Box 19024, Seattle, WA 98109, USA; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancer Cell. 2017 Mar 13;31(3):311-325. doi: 10.1016/j.ccell.2017.02.008.
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, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.
实体瘤中的T细胞功能障碍由多种机制导致。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重大障碍。细胞功能和存活的代谢限制塑造了肿瘤进展和免疫细胞功能。面对持续存在的抗原，慢性T细胞受体信号传导会使T淋巴细胞进入功能耗竭状态。在此，我们将重点讨论黑色素瘤、胰腺癌和卵巢癌中肿瘤及其微环境如何影响T细胞运输和功能，并探讨科学进展如何有助于克服这些障碍。
