肿瘤中 T 细胞功能的代谢障碍。
Metabolic Barriers to T Cell Function in Tumors.
机构信息
Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt-Ingram Cancer Center, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt-Ingram Cancer Center, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232
出版信息
J Immunol. 2018 Jan 15;200(2):400-407. doi: 10.4049/jimmunol.1701041.
The metabolic programs that drive T cell functions are exquisitely sensitive to cell intrinsic and extrinsic factors, allowing T cells to respond in a fine-tuned manner to a variety of immune challenges and conditions. However, many of the factors essential for effector T cell function are perturbed in the tumor microenvironment, where oncogenic mutations drive unrestrained cancer cell growth that leads to excess nutrient consumption, excess waste excretion, and insufficient oxygen delivery. This imposes metabolic constraints on infiltrating cells that result in dysfunction and loss of potential antitumor activity in both naturally occurring as well as tailored T cells introduced as part of immunotherapy. In this review, we highlight the metabolic properties that characterize tumor-infiltrating T cells, the barriers within the metabolic landscape of the tumor microenvironment, and the opportunities and challenges they present in development of new cancer therapeutics.
驱动 T 细胞功能的代谢程序对细胞内在和外在因素极其敏感，使 T 细胞能够以精细的方式对各种免疫挑战和情况做出反应。然而，在肿瘤微环境中，许多效应 T 细胞功能所必需的因素受到干扰，致癌突变导致不受控制的癌细胞生长，导致营养消耗过多、废物排泄过多和供氧不足。这对浸润细胞施加了代谢限制，导致自然存在的以及作为免疫疗法一部分引入的定制 T 细胞的功能障碍和潜在抗肿瘤活性丧失。在这篇综述中，我们强调了表征浸润肿瘤的 T 细胞的代谢特性、肿瘤微环境代谢景观中的障碍，以及它们在开发新的癌症治疗方法方面带来的机遇和挑战。
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