Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer.
Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer.
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DOI：
10.1016/j.cell.2016.12.004
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发表时间：
2017-02-09
期刊：
影响因子：
64.5
通讯作者：
Glimcher LH
中科院分区：
文献类型：
--
作者：
Cubillos-Ruiz JR;Bettigole SE;Glimcher LH
恶性细胞利用不同的策略，使它们能够在不利条件下茁壮成长，同时抑制抗肿瘤免疫反应的发展。肿瘤块内的不利微环境条件，例如营养缺乏、氧限制、高代谢需求和氧化应激，干扰内质网（ER）的蛋白质折叠能力，从而引起“ER应激”的细胞状态。ER应激感受器的持续激活赋予恶性细胞更强的致瘤、转移和耐药能力。此外，最近的研究发现，ER应激反应通过操纵肿瘤微环境中骨髓细胞的功能进一步阻碍保护性抗癌免疫的发展。在这里，我们讨论了ER应激在癌症中的致瘤性和免疫调节作用，我们探讨了靶向ER应激反应的概念，以提高标准化疗的疗效，并在临床上不断发展癌症免疫疗法。
Malignant cells utilize diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting the development of anti-tumor immune responses. Hostile microenvironmental conditions within tumor masses, such as nutrient deprivation, oxygen limitation, high metabolic demand and oxidative stress disturb the protein folding capacity of the Endoplasmic Reticulum (ER), thereby provoking a cellular state of “ER stress”. Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic and drug resistant capacity. Additionally, recent studies have uncovered that ER stress responses further impede the development of protective anti-cancer immunity by manipulating the function of myeloid cells in the tumor microenvironment. Here, we discuss the tumorigenic and immunoregulatory effects of ER stress in cancer, and we explore the concept of targeting ER stress responses to enhance the efficacy of standard chemotherapies and evolving cancer immunotherapies in the clinic.