The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.
The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.
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DOI：
10.3389/fcell.2022.867341
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
内质网（ER）是一个大的连续的膜细胞器，它作为蛋白质和脂质合成的枢纽发挥着核心作用，而线粒体是能量产生的主要场所。T细胞是基于对蛋白质合成和分泌的需要以及与外源抗原识别和细胞毒性效应子应答相关的代谢灵活性而表现出对ER和线粒体功能的稳健依赖性的免疫亚群。在细胞-内质网接触位点（MERC）存在密切的连接，MERC通过调节分裂和融合以及葡萄糖、Ca 2+和脂质交换作为细胞代谢稳态的结构和生化平台。肿瘤免疫治疗领域的研究表明，肿瘤微环境中营养缺乏和肿瘤抗原刺激的复杂相互作用对ER和线粒体造成压力，导致细胞器结构功能障碍和代谢稳态丧失。在这里，我们评估了先前的文献，建立了这两个细胞器的结构界面是如何受到实体瘤的压力的影响，沿着在T细胞中MERC的细胞器稳态操纵的最新进展。这些发现提供了强有力的证据，证明使用独特的治疗途径增加肿瘤免疫力，重新充电T细胞中的细胞代谢稳态。
The endoplasmic reticulum (ER) is a large continuous membranous organelle that plays a central role as the hub of protein and lipid synthesis while the mitochondria is the principal location for energy production. T cells are an immune subset exhibiting robust dependence on ER and mitochondrial function based on the need for protein synthesis and secretion and metabolic dexterity associated with foreign antigen recognition and cytotoxic effector response. Intimate connections exist at mitochondrial-ER contact sites (MERCs) that serve as the structural and biochemical platforms for cellular metabolic homeostasis through regulation of fission and fusion as well as glucose, Ca2+, and lipid exchange. Work in the tumor immunotherapy field indicates that the complex interplay of nutrient deprivation and tumor antigen stimulation in the tumor microenvironment places stress on the ER and mitochondria, causing dysfunction in organellar structure and loss of metabolic homeostasis. Here, we assess prior literature that establishes how the structural interface of these two organelles is impacted by the stress of solid tumors along with recent advances in the manipulation of organelle homeostasis at MERCs in T cells. These findings provide strong evidence for increased tumor immunity using unique therapeutic avenues that recharge cellular metabolic homeostasis in T cells.
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影响因子：
15.9
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
影响因子：
3.3
作者：
BENTAL, M;DEUTSCH, C
通讯作者：
DEUTSCH, C
影响因子：
12.4
作者：
Adams JM;Cory S
通讯作者：
Cory S
DOI：
10.1073/pnas.1620433114
发表时间：
2017-01-31
影响因子：
11.1
作者：
Chamoto, Kenji;Chowdhury, Partha S.;Honjo, Tasuku
通讯作者：
Honjo, Tasuku