Ueda Gosei, Tamura Yasuaki, Hirai Itaru, Kamiguchi Kenjirou, Ichimiya Shingo, Torigoe Toshihiko, Hiratsuka Hiroyoshi, Sunakawa Hajime, Sato Noriyuki
Department of Pathology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8556, Japan.
Cancer Sci. 2004 Mar;95(3):248-53. doi: 10.1111/j.1349-7006.2004.tb02211.x.
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 DCs 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.
用自体肿瘤衍生的热休克蛋白（Hsp）进行疫苗接种，如Hsp70、Hsp90和gp96，已被证明能引发针对分离出这些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，并且最近已在APC上鉴定出Hsp受体。在这里，我们表明骨髓来源的树突状细胞（DC）能够内化HSP-肽复合物，并且肽通过主要组织相容性复合体（MHC）I类呈递途径由DC重新呈递。此外，用肿瘤衍生的HSP脉冲DC进行免疫以转运体相关抗原加工（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。本研究结果为Hsp70的有效交叉呈递活性提供了有力证据，这可用于为癌症患者开发新的更有效的免疫治疗策略。
