Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

被引:498
作者
Anderson, Kristin G. [1 ,2 ,3 ,4 ]
Stromnes, Ingunn M. [1 ,2 ]
Greenberg, Philip D. [1 ,2 ,3 ,4 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Mail Stop D3-100,POB 19024, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
[3] Univ Washington, Sch Med, Dept Med Oncol, Seattle, WA 98109 USA
[4] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98109 USA
关键词
FATTY-ACID SYNTHASE; HUMAN PANCREATIC-CANCER; FOCAL ADHESION KINASE; WNT/BETA-CATENIN PATHWAY; INDOLEAMINE 2,3-DIOXYGENASE; ANTITUMOR-ACTIVITY; ONCOGENIC KRAS; INTERLEUKIN-8; EXPRESSION; PROGNOSTIC-SIGNIFICANCE; RECEPTOR EXPRESSION;
D O I
10.1016/j.ccell.2017.02.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:311 / 325
页数:15
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