Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment.
Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment.
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DOI：
10.3389/fonc.2014.00107
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发表时间：
2014
影响因子：
4.7
通讯作者：
Lysaght J
中科院分区：
文献类型：
--
作者：
Mockler MB;Conroy MJ;Lysaght J
免疫系统在控制癌症的发生和发展中起着关键作用。T细胞活化是抗肿瘤免疫反应的核心，与细胞代谢的变化一致。幼稚T细胞主要需要ATP生成代谢谱，而增殖效应T细胞需要促进快速生长和增殖的合成代谢谱。此外，特定的T细胞亚群需要不同的能量和生物合成途径来匹配其功能需求。通常不利的肿瘤微环境可以通过改变所产生的细胞代谢来影响T细胞免疫应答。通过操纵细胞代谢途径来定制免疫反应可能为癌症免疫治疗提供令人兴奋的新选择。T细胞反应也可能通过代谢操纵来治疗肥胖相关炎症的并发症，这是一个快速增长的全球健康问题，也是许多恶性肿瘤的主要风险因素。在这篇综述中，T细胞在抗肿瘤免疫中的多种代谢要求进行了讨论，以及肿瘤微环境的深刻影响和可能的途径，以提高抗肿瘤免疫的操作。
The immune system has a key role to play in controlling cancer initiation and progression. T cell activation, which is central to anti-tumor immune responses, coincides with changes in cellular metabolism. Naïve T cells predominantly require an ATP generating metabolic profile, whereas proliferating effector T cells require anabolic metabolic profiles that promote rapid growth and proliferation. Furthermore, specific T cell subsets require distinct energetic and biosynthetic pathways to match their functional requirements. The often hostile tumor microenvironment can affect T cell immune responses by altering the resulting cellular metabolism. Tailoring immune responses by manipulating cellular metabolic pathways may provide an exciting new option for cancer immunotherapy. T cell responses might also be skewed via metabolic manipulation to treat the complications of obesity-associated inflammation, which is a rapidly growing global health problem and a major risk factor for many malignancies. In this review, the diverse metabolic requirements of T cells in anti-tumor immunity are discussed, as well as the profound influence of the tumor microenvironment and the possible avenues for manipulation to enhance anti-tumor immunity.