HSP110与肿瘤免疫

Heat shock protein 110 and tumor immunity

热休克蛋白(heat shock protein,HSP)是在细胞应激下显著高表达的蛋白质,对于蛋白质转运、折叠和解离起重要作用。其免疫学活性最引人注目,包括:作为分子伴侣来结合抗原多肽,经由抗原递呈细胞递呈给MHC分子进而诱导特异免疫;可作为危险信号启动固有免疫;是良好的免疫佐剂。比之其它HSP,HSP110做为一种效应显著的免疫佐剂,具有更强势的伴侣功能和多肽结合能力。近年较多基础研究提示HSP110增强了相关肿瘤表位多肽、肿瘤相关抗原的特异性肿瘤免疫和抗肿瘤效应。此外,关于肾癌、黑色素瘤的双盲多中心Ⅱ及Ⅲ期临床试验提示HSP抗原肽复合物在肿瘤免疫治疗中安全有效。在此我们综述了HSP110的免疫学功能和肿瘤免疫中的应用。

Heat shock protein （HSP） is highly expressed in cells under stress, and plays an important role in protein transport, protein folding and protein dissociation. The immunologic competence is the most striking function of HSP. As molecular chaperone, HSP can bind antigen peptide to form a compound, which was presented to class MHC- I molecules by antigen presenting cells, contributing to the induction of specific T lymphocytes; as a danger signal, HSP also initiates innate immunity. HSP110 has stronger molecular chaperone function, and stronger polypeptide binding ability, comparing with other HSPs. Moreover, heat shock protein has been used as an adjuvant concerning its notable immunogenicity. Experimental studies have demonstrated that HSP110 can enhance specific tumor immunity and anti-tumor effects of related tumor epitope polypeptides and tumor antigens. More studies have confirmed that HSP antigen peptide complex is safe and effective in tumor immunotherapy. Clinical researches show that HSP antigen peptide complex has obvious advantages in the treatment of patients with renal cell carcinoma and melanoma in the double-blind and muhicenter clinical trials. Here, we reviewed the immunological function of HSP110 and its role in tumor immunity.