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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

References

    1. Baitsch L, Baumgaertner P, Devevre E, Raghav SK, Legat A, Barba L, Wieckowski S, Bouzourene H, Deplancke B, Romero P, et al. Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients. J Clin Invest. 2011;121:2350–2360. - PMC - PubMed
    1. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 2012;21:822–835. - PMC - PubMed
    1. Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, Chew A, Zhao Y, Levine BL, Albelda SM, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer immunology research. 2014;2:112–120. - PMC - PubMed
    1. Becker JC, Andersen MH, Schrama D, Thor Straten P. Immune-suppressive properties of the tumor microenvironment. Cancer Immunol Immunother. 2013;62:1137–1148. - PMC - PubMed
    1. Benabdellah K, Munoz P, Cobo M, Gutierrez-Guerrero A, Sanchez-Hernandez S, Garcia-Perez A, Anderson P, Carrillo-Galvez AB, Toscano MG, Martin F. Lent-On-Plus Lentiviral vectors for conditional expression in human stem cells. Sci Rep. 2016;6:37289. - PMC - PubMed

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