文章：

肿瘤发生和治疗过程中氨基酸分解代谢的免疫控制

Immune control by amino acid catabolism during tumorigenesis and therapy

原文发布日期：2019-01-29

DOI: 10.1038/s41568-019-0106-z

类型: Review Article

开放获取: 否

英文摘要：

Immune checkpoints arise from physiological changes during tumorigenesis that reprogramme inflammatory, immunological and metabolic processes in malignant lesions and local lymphoid tissues, which constitute the immunological tumour microenvironment (TME). Improving clinical responses to immune checkpoint blockade will require deeper understanding of factors that impact local immune balance in the TME. Elevated catabolism of the amino acids tryptophan (Trp) and arginine (Arg) is a common TME hallmark at clinical presentation of cancer. Cells catabolizing Trp and Arg suppress effector T cells and stabilize regulatory T cells to suppress immunity in chronic inflammatory diseases of clinical importance, including cancers. Processes that induce Trp and Arg catabolism in the TME remain incompletely defined. Indoleamine 2,3 dioxygenase (IDO) and arginase 1 (ARG1), which catabolize Trp and Arg, respectively, respond to inflammatory cues including interferons and transforming growth factor-β (TGFβ) cytokines. Dying cells generate inflammatory signals including DNA, which is sensed to stimulate the production of type I interferons via the stimulator of interferon genes (STING) adaptor. Thus, dying cells help establish local conditions that suppress antitumour immunity to promote tumorigenesis. Here, we review evidence that Trp and Arg catabolism contributes to inflammatory processes that promote tumorigenesis, impede immune responses to therapy and might promote neurological comorbidities associated with cancer.

摘要翻译： 

免疫检查点源于肿瘤发生过程中的生理变化，这些变化重编程了恶性病变区域及局部淋巴组织中的炎症、免疫及代谢过程，从而构成了免疫性肿瘤微环境（TME）。提高对免疫检查点阻断的临床反应，需要更深入地理解影响TME局部免疫平衡的因素。氨基酸色氨酸（Trp）和精氨酸（Arg）的分解代谢增强是癌症临床表现中TME的常见特征。分解代谢Trp和Arg的细胞通过抑制效应T细胞并稳定调节T细胞，在包括癌症在内的临床重要慢性炎症性疾病中抑制免疫反应。诱导TME中Trp和Arg分解代谢的过程仍未完全明确。分别催化Trp和Arg分解代谢的吲哚胺2,3-双加氧酶（IDO）和精氨酸酶1（ARG1）会对干扰素和转化生长因子-β（TGFβ）等炎症信号产生响应。垂死细胞产生的炎症信号（包括DNA）可通过干扰素基因刺激因子（STING）接头蛋白被感知，从而刺激I型干扰素的产生。因此，垂死细胞有助于建立抑制抗肿瘤免疫并促进肿瘤发生的局部条件。本文综述了证据表明Trp和Arg的分解代谢参与促进肿瘤发生、阻碍治疗免疫反应并可能加剧癌症相关神经共病的炎症过程。

原文链接：

Immune control by amino acid catabolism during tumorigenesis and therapy