title: Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity.
abstract: 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.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Gosei
authors.initials: G
authors.lastname: Ueda
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Itaru
authors.initials: I
authors.lastname: Hirai
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Kamiguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hiratsuka
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunakawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D034801:Mastocytoma / Q000276:immunology*; D051379:Mice; D018613:Microscopy, Confocal; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I