HSP90及其抑制剂对肿瘤免疫反应的影响

HSP90作为一种热休克蛋白参与调控蛋白质的正确折叠、装配和水解等多种生理过程,其在肿瘤组织中异常表达与活化,与恶性肿瘤的发生发展密切相关,是肿瘤药物研发的重要靶标,目前已有多个HSP90抑制剂进入临床研究。近年来研究发现,HSP90在调控机体固有性免疫和适应性免疫反应中也发挥着重要的作用,包括抗原呈递、T细胞、NK细胞活化和DC(树突状细胞)的成熟,以及肿瘤微环境的免疫抑制等。抑制HSP90导致免疫抑制和免疫激活双重反应,因此,HSP90在机体免疫中作用复杂,有待人们进一步研究。本文主要综述了HSP90及其抑制剂与肿瘤免疫之间的联系,为今后相关研究人员的工作提供参考。

The Influences of HSP90 and Its Inhibitors on Tumor Immune Reactions

ABSTRACT: HSP90 is one of heat shock proteins (HSPs) involving in various physiological processes with abilities of guiding the normal folding, assembling and hydrolysis of many key proteins. A variety of tumor tissues have abnormal expression and activation of HSP90, which is correlated with tumorigenesis and malignant progression. HSP90 has become an important target for anticancer drug de- velopment and there have been some HSP90 inhibitors entered into the clinical research. Recent studies have found that HSP90 has been revealed to play important roles in regulating the innate and adaptive immune responses, including antigen presentation, activation of T lymphocyte cell and NK cell, maturation of dendritic cells, as well as immunosuppression in tumor microenvironment. Inactivation of HSP90 induces both immunosuppression and immunostimulation. Hence, the intricate function of HSP90 in organism immunoregulation is not very clear and further study is needed. Here, the association between the HSP90 and cancer immune surveillance were reviewed, providing a reference for researchers'' future study.