Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Trends Immunol. 2019 Feb;40(2):128-141. doi: 10.1016/j.it.2018.12.001. Epub 2019 Jan 3.
Protective anti-tumor immune responses are mediated by effector molecules that enable successful elimination of malignant cells. As the site where transmembrane and secreted proteins are generated, the endoplasmic reticulum (ER) of immune cells plays a key role in this process. Recent studies have indicated that adverse conditions within tumors perturb ER homeostasis in infiltrating immune cells, which can impede the development of effective anti-cancer immunity. Here, we describe how the tumor microenvironment induces ER stress in immune cells, and discuss the detrimental consequences of persistent ER stress responses in intratumoral immune populations. We also explore the concept of targeting ER stress responses to reinvigorate endogenous anti-tumor immunity and enhance the efficacy of various forms of cancer immunotherapy.
保护性抗肿瘤免疫反应是由效应分子介导的，这些分子能够成功清除恶性细胞。作为跨膜和分泌蛋白产生的场所，免疫细胞的内质网（ER）在这个过程中起着关键作用。最近的研究表明，肿瘤内的不利条件会扰乱浸润免疫细胞中的 ER 稳态，从而阻碍有效的抗肿瘤免疫的发展。在这里，我们描述了肿瘤微环境如何诱导免疫细胞中的 ER 应激，并讨论了肿瘤内免疫群体中持续的 ER 应激反应的有害后果。我们还探讨了靶向 ER 应激反应以重新激活内源性抗肿瘤免疫并增强各种形式癌症免疫疗法疗效的概念。
