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* Department of Dermatology, University Hospital of Erlangen, Hartmannstra
e 14, Erlangen, Germany;
Ludwig Institute for Cancer Research, Brussels, Belgium;
Laboratory of Physiology, Medical School, Free University of Brussels, Brussels, Belgium; and
Department of Dermatology and Allergology, University Hospital Giessen and Marburg, Deutschhausstrae 9, Marburg, Germany
To avoid immune escape by down-regulation or loss of Ag by the tumor cells, target Ags are needed, which are important for the malignant phenotype and survival of the tumor. We could identify a CD4+ T cell epitope derived from the human melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high m.w.-melanoma-associated Ag), which is strongly expressed on >90% of human melanoma lesions and is important for the motility and invasion of melanoma cells. However, MCSP is not strictly tumor specific, because it is also expressed in a variety of normal tissues. Therefore, self tolerance should prevent the induction of strong T cell responses against these Ags by vaccination strategies. In contrast, breaking self tolerance to this Ag by effectively manipulating the immune system might mediate antitumor responses, although it would bear the risk of autoimmunity. Surprisingly, we could readily isolate CD4+ Th cells from the blood of a healthy donor-recognizing peptide MCSP693–709 on HLA-DR11-expressing melanoma cells. Broad T cell reactivity against this Ag could be detected in the peripheral blood of both healthy donors and melanoma patients, without any apparent signs of autoimmune disease. In some patients, a decline of T cell reactivity was observed upon tumor progression. Our data indicate that CD4+ T cells are capable of recognizing a membrane glycoprotein that is important in melanoma cell function, and it may be possible that the sizable reactivity to this Ag in most normal individuals contributes to immune surveillance against cancer.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Wilhelm-Sander-Stiftung, the Deutsche Forschungsgemeinschaft (Schu 1264 2-3 and SFB 643 Project C1), and the European Union (Cancerimmunotherapy, contract no. 518234).
2 Address correspondence and reprint requests to Dr. Erwin S. Schultz, Department of Dermatology and Allergology University Hospital Giessen and Marburg, Deutschhausstrae 9, Marburg, Germany. E-mail address: eschultz{at}med.uni-marburg.de
3 Abbreviations used in this paper: MCSP, melanoma-associated chondroitin sulfate proteoglycan; MT3-MMP, membrane-type 3 matrix metalloproteinase; EBV-B, EBV-transformed B; DC, dendritic cells; Ii, invariant chain; qPCR, quantitative real-time PCR; LN, lymph nodes.
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