International Immunology Advance Access published online on January 10, 2005
International Immunology, doi:10.1093/intimm/dxh203
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1 Clinical Cooperation Group on Hyperthermia, Internal Medicine Department III, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany
* To whom correspondence should be addressed. Heat shock has been shown to have pleiotropic effects on tumor physiology besides a direct cytotoxic effect. In the present study, we address the question whether heat shock treatment has an impact on the antigenicity of human melanoma cells and their specific recognition by cytotoxic lymphocytes. The heat shock response was induced by treating the cells with two different thermal isoeffect doses, which resulted in equivalent clonogenic survival, mimicking doses achieved during clinical hyperthermia treatment of tumors. Antigen expression and immune recognition by cytotoxic T cells was studied using the human melanoma cell lines 624.38-MEL, SK-MEL23, WM115 and WM266-4, which naturally express, process and present tyrosinase and Melan-A/MART-1-derived peptides in the context of HLA-A2 molecules. We demonstrate that during the heat shock response following the two thermal doses, heat shock protein 70 (Mr 72 kDa) (HSP70) was induced with differential kinetics; tyrosinase protein and mRNA levels dissociated with a significant increase in tyrosinase protein and a decrease in transcript levels. A similar dissociation was not observed for Melan-A/MART-1. Furthermore, tyrosinase-specific T-cell recognition did not correlate with changes in HSP70 and antigen protein levels. These results suggest that caution has to be taken when considering protein levels as a marker for the antigenic status of a tumor. Moreover, these results document the maintenance of immunological homeostasis during recovery from heat treatment, thus challenging the view that tumor cells subjected to heat shock become resistant to CTL recognition.
Received November 9, 2003
Accepted December 7, 2004
Article
Melanoma-associated antigen tyrosinase but not Melan-A/MART-1 expression and presentation dissociate during the heat shock response
2 Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Marchioninistrasse 25, 81377 Munich, Germany
Elfriede Noessner, E-mail: noessner{at}gsf.de
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