Milani, V. and Noessner, E. and Ghose, S. and Kuppner, M. and Ahrens, B. and Scharner, A. and Gastpar, R. and Issels, R. D. (2002) Heat shock protein 70: role in antigen presentation, and immune stimulation. INTERNATIONAL JOURNAL OF HYPERTHERMIA, 18 (6). pp. 563-575. ISSN 0265-6736, 1464-5157
Full text not available from this repository. (Request a copy)Abstract
Heat shock proteins (HSP) when released into the extracellular milieu can act simultaneously as a source of antigen due to their ability to chaperone peptides and as a maturation signal for dendritic cells, thereby inducing DCs to cross-present antigens to CD8+ T-cells. HSP can also act independently from associated peptides, stimulating the innate immune system. Previous results regarding the activation of NK cells by HSP70 cell surface expression on tumour cells and soluble HSP70 will be further covered elsewhere within this issue. For cross-presentation, HSP70-peptide complexes (HSP70-PC) were used from two human melanoma cell lines that differ in the expression of the tumour-associated antigen tyrosinase. Purified HSP70-PC consists of both the constitutively expressed HSC70 and the inducible HSP70. HSP70-peptide complexes purified from tyrosinase positive (HSP70-PC/tyr(+)) human melanoma cells, incubated with immature DCs, results in the activation of HLA-*A0201-restricted tyrosinase peptide-specific T-cells. Receptor-mediated uptake of HSP70-PC by DCs and intracellular transport are required for efficient MHC class I restricted cross-presentation of chaperoned peptides. Demonstration of HSP70-PC mediated cross-presentation of such non-mutated naturally expressed tumour antigens is of special clinical interest with regard to hyperthermia. Tumour regression and improved local control have been shown within clinical phase II/III trials integrating regional hyperthermia combined with radiation and/or chemotherapy in multimodal treatment strategies. According to the proposed concept, local necrosis induced by hyperthermic treatment induces the release of HSPs, followed by uptake, processing and presentation of associated peptides by DCs. By acting as chaperone and a signal for DC maturation, HSP70-PC might efficiently prime circulating T-cells. Therefore, upregulating HSP70 and causing local necrosis in turnout tissue by hyperthermia offers great potential as a new approach to directly activate the immune system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TOLL-LIKE RECEPTORS; DENDRITIC CELL MATURATION; CYTOTOXIC T-LYMPHOCYTES; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS; LPS BINDING-PROTEIN; LIPOPOLYSACCHARIDE LPS; MOLECULAR CHAPERONES; TUMOR IMMUNOGENICITY; SIGNALING PATHWAYS; antigen presentation; dendritic cells; human model; tumour immunity; Toll-like receptor; hyperthermia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Aug 2021 12:58 |
| Last Modified: | 26 Aug 2021 12:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39724 |
Actions (login required)
 |
View Item |
