Metabolic reprogramming and apoptosis sensitivity: Defining the contours of a T cell response. (1st November 2017)

• Record Type: Journal Article
• Authors: Voss, Kelsey; Larsen, Sasha E.; Snow, Andrew L.
• Is Part Of: Cancer letters. Volume 408(2017)
• Page Start: 190
• Page End: 196
• Publication Date: 2017-11-01
• Subjects: Immunometabolism -- Apoptosis -- T cells -- Restimulation-induced cell death -- Cytokine withdrawal-induced cell death -- CWID; AICD Activation-induced cell death -- Bcl-2 B cell lymphoma 2 -- BH3 Bcl-2 domain homology 3 -- CM Central memory -- COX Cytochrome c oxidase -- CWID Cytokine withdrawal-induced death -- EM Effector memory -- FasL Fas ligand -- FAO Fatty acid oxidation -- FASN Fatty acid synthase -- IL-2 Interleukin-2 -- IL-7 Interleukin-7 -- Mtb Mycobacterium tuberculosis -- OXPHOS Oxidative phosphorylation -- PPP Pentose phosphate pathway -- PD-1 Programmed death-1 -- ROS Reactive oxygen species -- Tregs Regulatory T cells -- RICD Restimulation-induced cell death -- SLAM Signaling lymphocyte activation molecule -- SRC Spare respiratory capacity -- T-ALL T cell acute lymphoblastic leukemia -- TCR T cell receptor -- TCA cycle Tricarboxylic acid cycle -- TIL Tumor infiltrating lymphocytes -- XLP-1 X-linked lymphoproliferative disease; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.08.033
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: An effective adaptive immune response hinges on the rapid clonal expansion of T cells in response to antigen. The sensitivity of these T cells to programmed cell death (i.e. apoptosis) is carefully calibrated at various stages to ensure a robust yet measured reaction that resolves without inflicting unintended damage to host tissues. To meet bioenergetic demands associated with vigorous proliferation, acquisition of effector functions, and memory formation, T cells also undergo dynamic changes in their metabolism at every stage of this response. In this review, we focus on relatively recent studies that illuminate intimate links between metabolic programs and apoptosis sensitivity in T cells. We then examine how these connections ultimately influence T cell survival and function within the metabolically taxing environs of the tumor microenvironment. Highlights: T cells demonstrate dynamic reprogramming of their metabolism as an adaptive immune response unfolds. The magnitude of any T cell response is governed both by proliferation and apoptosis. Changes in T cell metabolism directly influence apoptosis sensitivity to regulate immunological memory and homeostasis. Stressful conditions of the tumor microenvironment force T cells to adapt their metabolism or succumb to apoptosis. Understanding these metabolic adaptations and their influence on T cell death may inform and improve new immunotherapies.