Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells.
Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells.
复制标题
肿瘤微环境诱导的自然杀伤细胞免疫代谢重编程。
DOI：
10.3389/fimmu.2018.02517
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Matosevic S
中科院分区：
文献类型：
--
作者：
Chambers AM;Lupo KB;Matosevic S
能量代谢是促进肿瘤生长、发展和转移的关键。同时，细胞代谢也在肿瘤微环境中介导免疫细胞的存活、增殖和细胞毒反应。自然杀伤细胞根除肿瘤的能力依赖于它们在抗肿瘤效应活动期间在功能上持续的能力。然而，肿瘤代谢需求的改变会导致细胞因子激活的自然杀伤细胞的功能反应受损，从而导致过继细胞免疫治疗的有效性降低。肿瘤通过许多机制发挥这些免疫抑制作用，其中一个关键驱动因素是缺氧。低氧还会促进与癌症相关的胞外酶CD39和CD73产生腺苷。腺苷的免疫抑制表现为增殖减少和抗肿瘤功能受损，腺苷能信号成为免疫代谢检查点阻断的靶点。了解这种免疫代谢抑制对于指导新一代基于自然杀伤细胞的免疫疗法的工程至关重要，这种免疫疗法能够更有效地针对难以治疗的实体肿瘤。
Energy metabolism is key to the promotion of tumor growth, development, and metastasis. At the same time, cellular metabolism also mediates immune cell survival, proliferation and cytotoxic responses within the tumor microenvironment. The ability of natural killer cells to eradicate tumors relies on their ability to functionally persist for the duration of their anti-tumor effector activity. However, a tumor's altered metabolic requirements lead to compromised functional responses of cytokine-activated natural killer cells, which result in decreased effectiveness of adoptive cell-based immunotherapies. Tumors exert these immunosuppressive effects through a number of mechanisms, a key driver of which is hypoxia. Hypoxia also fuels the generation of adenosine from the cancer-associated ectoenzymes CD39 and CD73. Adenosine's immunosuppression manifests in decreased proliferation and impaired anti-tumor function, with adenosinergic signaling emerging as an immunometabolic checkpoint blockade target. Understanding such immunometabolic suppression is critical in directing the engineering of a new generation of natural killer cell-based immunotherapies that have the ability to more effectively target difficult-to-treat solid tumors.
登录
查看更多内容
影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
影响因子：
7.3
作者：
Ali AK;Nandagopal N;Lee SH
通讯作者：
Lee SH
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
11.2
作者：
Cekic C;Day YJ;Sag D;Linden J
通讯作者：
Linden J
影响因子：
1.2
作者：
Figueiredo, Ana Sofia;Killian, Doreen;Lindner, Holger A.
通讯作者：
Lindner, Holger A.