Voss Kelsey, Larsen Sasha E, Snow Andrew L
Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Infectious Disease Research Institute, Seattle, WA, USA.
Cancer Lett. 2017 Nov 1;408:190-196. doi: 10.1016/j.canlet.2017.08.033. Epub 2017 Sep 1.
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.
有效的适应性免疫反应取决于T细胞对抗原的快速克隆扩增。这些T细胞对程序性细胞死亡(即凋亡)的敏感性在各个阶段都经过精心校准,以确保产生一种强大而适度的反应,该反应能够消退而不会对宿主组织造成意外损伤。为了满足与旺盛增殖、获得效应功能和形成记忆相关的生物能量需求,T细胞在这种反应的每个阶段其代谢也会发生动态变化。在这篇综述中,我们重点关注了一些相对较新的研究,这些研究揭示了T细胞代谢程序与凋亡敏感性之间的密切联系。然后,我们研究了这些联系如何最终影响T细胞在肿瘤微环境这种代谢负担较重的环境中的存活和功能。