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

Kristin G Anderson, Ingunn M Stromnes, Philip D Greenberg

Journal: Cancer cell 2017;31(3):311-325

PMID: 28292435

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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.

Address: 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. Electronic address: [email protected].; 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. Electronic address: [email protected].

DOI: 10.1016/j.ccell.2017.02.008

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MeSH Terms: Amino Acids, Cytotoxicity, Immunologic, Fatty Acids, Genes, p53, Glucose, Humans, Lactic Acid, Neoplasms, Receptors, Antigen, T-Cell, T-Lymphocytes, Tumor Microenvironment