Stress relief for cancer immunotherapy: implications for the ER stress response in tumor immunity.

Stress relief for cancer immunotherapy: implications for the ER stress response in tumor immunity.
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DOI:
10.1007/s00262-020-02740-3
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发表时间:
2021-05
期刊:
Cancer immunology, immunotherapy : CII
影响因子:
--
通讯作者:
Thaxton JE
Thaxton JE
中科院分区:
其他
文献类型:
--
作者:
Andrews AM;Tennant MD;Thaxton JE

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实体瘤微环境充满了对浸润免疫细胞施加压力的因素。内质网(ER)应激传感器PKR ER样激酶(PERK)被启动以感知和响应由细胞应激物诱导的ER腔中错误折叠蛋白质的负荷。PERK作为对细胞应激的急性和慢性反应的主调节剂以及在细胞代谢的调节中的作用已被记录。在这里,我们提供了一个概述PERK的作用的基础上,什么是已知的,仍然是在肿瘤中的免疫细胞和肿瘤控制的影响进行测试。PERK是能够优先诱导活化转录因子4(ATF 4)作为对细胞应激的响应的几种ER激酶之一。ATF4协调氧化应激反应并控制氨基酸代谢。我们讨论了ATF4在肿瘤免疫中的测试作用,并提供了对ATF4在实体瘤应激中可能发挥的双重保护和有害作用的见解。
The solid tumor microenvironment is replete with factors that present a stress to infiltrating immune cells. Endoplasmic reticulum (ER) stress sensor PKR ER-like kinase (PERK) is primed to sense and response to the burden of misfolded proteins in the ER lumen induced by cell stressors. PERK has documented roles as a master regulator of acute and chronic responses to cell stress as well as in the regulation of cell metabolism. Here we provide an overview of the roles of PERK based on what is known and remains to be tested in immune cells in tumors and impacts on tumor control. PERK is one of several ER kinases able to preferentially induce activating transcription factor 4 (ATF4) as a response to cell stress. ATF4 orchestrates the oxidative stress response and governs amino acid metabolism. We discuss the tested role of ATF4 in tumor immunity and provide insight on the dueling protective and deleterious roles that ATF4 may play in the stress of solid tumors.
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