Immunomodulating activity of mycobacterial heat shock protein 65 in tumor cells.
In recent years, heat shock proteins have been shown to be effective in enhancing the immunogenicity of tumors. In this study, we examined the effect of mycobacterial hsp65 gene transfection in a non-immunogenic and aggressive tumor cell-line in order to understand the factors that could contribute to the increase in immunogenicity mediated by Hsp65. The transfected cells were found to have indeed lost their tumorigenenicity and increased their immunogenicity. Tumor-specific cytotoxic T cells were present only in mice immunized with the Hsp65-expressing cells. Furthermore, endogenous Hsp70 was significantly increased in irradiated Hsp65-expressing cells and recombinant Hsp65 protein was able to stimulate the mRNA expression of various T helper 1 (Th1) and pro-inflammatory cytokines in splenocyte cultures, as well as a modest expansion of CD4 T cells. These results provide further evidence of the immunomodulating properties of Hsp65, which could be exploited for the treatment of cancer.
Tan
B H
BH
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Wang
L
L
Gan
Y H
YH
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins