Beckermann Kathryn E, Dudzinski Stephanie O, Rathmell Jeffrey C
Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, 2220 Pierce Avenue, Nashville, TN 37232, USA.
Department of Biomedical Engineering, 2301 Vanderbilt Place, Nashville, TN 37235, USA.
Cytokine Growth Factor Rev. 2017 Jun;35:7-14. doi: 10.1016/j.cytogfr.2017.04.003. Epub 2017 Apr 23.
Metabolic and signaling pathways are integrated to determine T cell fate and function. As stimulated T cells gain distinct effector functions, specific metabolic programs and demands are also adopted. These changes are essential for T cell effector function, and alterations or dysregulation of metabolic pathways can modulate T cell function. One physiological setting that impacts T cell metabolism is the tumor microenvironment. The metabolism of cancer cells themselves can limit nutrients and accumulate waste products. In addition to the expression of inhibitory ligands that directly modify T cell physiology, T cell metabolism may be strongly inhibited in the tumor microenvironment. This suppression of T cell metabolism may inhibit effector T cell activity while promoting suppressive regulatory T cells, and act as a barrier to effective immunotherapies. A thorough understanding of the effect of the tumor microenvironment on the immune system will support the continued improvement of immune based therapies for cancer patients.
代谢和信号通路相互整合，以决定T细胞的命运和功能。随着受刺激的T细胞获得不同的效应功能，特定的代谢程序和需求也会被采用。这些变化对于T细胞的效应功能至关重要，代谢途径的改变或失调会调节T细胞功能。影响T细胞代谢的一个生理环境是肿瘤微环境。癌细胞自身的代谢会限制营养物质并积累代谢废物。除了表达直接改变T细胞生理的抑制性配体外，T细胞代谢在肿瘤微环境中可能会受到强烈抑制。T细胞代谢的这种抑制可能会抑制效应T细胞的活性，同时促进抑制性调节性T细胞，从而成为有效免疫疗法的障碍。深入了解肿瘤微环境对免疫系统的影响，将有助于持续改进针对癌症患者的免疫疗法。
