Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity
Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity
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DOI：
10.1111/j.1349-7006.2004.tb02211.x
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发表时间：
2004-03-01
期刊：
影响因子：
5.7
通讯作者：
Sato, N
中科院分区：
文献类型：
--
作者：
Ueda, G;Tamura, Y;Sato, N
已证明，使用自体肿瘤来源的热休克蛋白 (Hsp)（例如 Hsp70、Hsp90 和 gp96）进行疫苗接种可引发针对分离出 Hsp 的肿瘤的特异性免疫反应。 Hsp免疫的效果完全取决于免疫宿主中功能性抗原呈递细胞（APC）的存在，并且APC上的Hsp受体最近已被鉴定。在这里，我们证明骨髓来源的树突状细胞（DC）能够内化HSP-肽复合物，并且肽由DC通过主要组织相容性复合物（MHC）I类呈递途径重新呈递。此外，用肿瘤源性 HSP 脉冲的 IDC 进行免疫，会以转运蛋白相关抗原加工 (TAP) 依赖性方式诱导针对多种抗原肽的强烈细胞毒性 T 细胞 (CTL) 反应。本研究的结果提供了强有力的证据，证明 Hsp70 具有有效的交叉启动活性，可用于为癌症患者开发新的、更有效的免疫治疗策略。
Vaccination with autologous tumor-derived heat shock proteins (Hsp), such as Hsp70, Hsp90 and gp96, has been demonstrated to elicit specific immune responses against the tumor from which the Hsps were isolated. The effect of Hsp immunization is wholly dependent on the presence of functional antigen-presenting cells (APCs) in the immunized host, and Hsp receptors on APCs have recently been identified. Here we show that bone marrow-derived dendritic cells (DCs) are able to internalize HSP-peptide complex and that peptides are re-presented by DCs via the major histocompatibility complex (MHC) class I presentation pathway. In addition, immunization with tumor-derived HSP-pulsed IDCs induces strong cytotoxic T cell (CTL) responses against multiple antigenic peptides in a transporter-associated antigen processing (TAP)-dependent manner. The results of the present study provide strong evidence of an efficient cross-priming activity of Hsp70, which could be exploited in the development of new and more effective immunotherapeutic strategies for cancer patients.