Graner Michael W
Department of Neurosurgery, University of Colorado Denver, Aurora, Colorado, USA.
Adv Cancer Res. 2016;129:191-224. doi: 10.1016/bs.acr.2015.10.001. Epub 2015 Nov 3.
Heat-shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays prominent functional roles in nearly all aspects of cell biology. As a chaperone, it interacts with literally hundreds of "clients," many of which are important drivers, regulators, and promoters of cancer. Thus, HSP90 is a high-value target in the development of anticancer therapeutics. Despite its popularity, our overall knowledge of HSP90 in immune function has lagged behind its well-recognized tumor-supportive roles. The use of inhibitors of HSP90 as chemical biological probes has been invaluable in revealing important roles for the chaperone in multiple aspects of immune function. Given this critical link, we must now consider the question of how immune outcomes may be affected by the HSP90 inhibitors currently in clinical development for the treatment of cancer. This chapter will review some of the immunological aspects of HSP90 function in terms of its intracellular and extracellular roles in antigen presentation, immune effector cell tasks, and regulation of inflammatory processes. This review will further examine the value of HSP90 inhibitors within the context of cancer immunotherapy and will discuss how these drugs might be optimally utilized in combination with immune stimulatory approaches against cancer.
热休克蛋白90（HSP90）是一种高度保守的分子伴侣，在细胞生物学的几乎所有方面都发挥着重要的功能作用。作为一种伴侣蛋白，它实际上与数百种“客户”相互作用，其中许多是癌症的重要驱动因素、调节因子和促进因子。因此，HSP90是抗癌治疗药物开发中的一个高价值靶点。尽管它很受关注，但我们对HSP90在免疫功能方面的整体认识仍落后于其广为人知的肿瘤支持作用。使用HSP90抑制剂作为化学生物学探针，对于揭示该伴侣蛋白在免疫功能多个方面的重要作用具有重要价值。鉴于这一关键联系，我们现在必须考虑一个问题，即目前正在临床开发用于治疗癌症的HSP90抑制剂可能如何影响免疫结果。本章将从HSP90在抗原呈递、免疫效应细胞任务和炎症过程调节中的细胞内和细胞外作用等方面，综述其免疫功能的一些免疫学方面。本综述将进一步探讨HSP90抑制剂在癌症免疫治疗背景下的价值，并将讨论如何将这些药物与针对癌症的免疫刺激方法最佳地联合使用。
