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Immunology |
1 Insitute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark; 2 Institute for Cell Research, University of Würzburg, Würzburg, Germany; 3 Skin Cancer Unit, German Cancer Research Center Heidelberg, Mannheim, Germany; 4 Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany; 5 Department of Dermatology, Campus Charité Mitte, Berlin, Germany; and 6 Department of Dermatology and Dermato-Oncology, University of Würzburg, Würzburg, Germany
Activating BRAF somatic missense mutations within the kinase domain are present in 60–66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.
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