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Review
. 2017 Mar 13;31(3):311-325.
doi: 10.1016/j.ccell.2017.02.008.

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

Kristin G Anderson  1 , Ingunn M Stromnes  2 , Philip D Greenberg  3
Affiliations
Review

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

Kristin G Anderson et al. Cancer Cell. .

Abstract

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.

Keywords: T cell dysfunction; TME; adoptive T cell therapy; genetic engineering; immunotherapy; tumor microenvironment.

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Figures

Figure 1
Figure 1
Overview of obstacles in the tumor microenvironment that interfere with T cell trafficking and function.
Figure 2
Figure 2
Metabolic perturbations within tumor cells modulate the tumor microenvironment to limit nutrient availability and generate metabolic byproducts that suppress T cell function.
Figure 3
Figure 3
Drivers of T cell dysfunction in tumors.
See this image and copyright information in PMC

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