Article

Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity.

Department of Pathology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8556, Japan.
Cancer Science (impact factor: 3.33). 04/2004; 95(3):248-53. pp.248-53
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
30 Views
  • Source
    Article: Trogocytosis of MHC-I/peptide complexes derived from tumors and infected cells enhances dendritic cell cross-priming and promotes adaptive T cell responses.
    Qian-Jin Zhang, Xiao-Lin Li, David Wang, Xiao-Cong Huang, J Michael Mathis, Wei-Ming Duan, David Knight, Runhua Shi, Jonathan Glass, Dong-Qing Zhang, Lea Eisenbach, Wilfred A Jefferies
    [show abstract] [hide abstract]
    ABSTRACT: The transporter associated with antigen processing (TAP) and the major histocompatibility complex class I (MHC-I), two important components of the MHC-I antigen presentation pathway, are often deficient in tumor cells. The restoration of their expression has been shown to restore the antigenicity and immunogenicity of tumor cells. However, it is unclear whether TAP and MHC-I expression in tumor cells can affect the induction phase of the T cell response. To address this issue, we expressed viral antigens in tumors that are either deficient or proficient in TAP and MHC-I expression. The relative efficiency of direct immunization or immunization through cross-presentation in promoting adaptive T cell responses was compared. The results demonstrated that stimulation of animals with TAP and MHC-I proficient tumor cells generated antigen specific T cells with greater killing activities than those of TAP and MHC-I deficient tumor cells. This discrepancy was traced to differences in the ability of dendritic cells (DCs) to access and sample different antigen reservoirs in TAP and MHC-I proficient versus deficient cells and thereby stimulate adaptive immune responses through the process of cross-presentation. In addition, our data suggest that the increased activity of T cells is caused by the enhanced DC uptake and utilization of MHC-I/peptide complexes from the proficient cells as an additional source of processed antigen. Furthermore, we demonstrate that immune-escape and metastasis are promoted in the absence of this DC 'arming' mechanism. Physiologically, this novel form of DC antigen sampling resembles trogocytosis, and acts to enhance T cell priming and increase the efficacy of adaptive immune responses against tumors and infectious pathogens.
    PLoS ONE 02/2008; 3(8):e3097. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

autologous tumor-derived heat shock proteins
 
bone marrow-derived dendritic cells
 
cancer patients
 
effective immunotherapeutic strategies
 
elicit specific immune responses
 
functional antigen-presenting cells
 
internalize HSP-peptide complex
 
major histocompatibility complex
 
multiple antigenic peptides
 
transporter-associated antigen processing
 
tumor
 
tumor-derived HSP-pulsed DCs induces strong cytotoxic T cell
 
Vaccination