Abstract
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 (V599E)BRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the (V599E)BRAF genotype during progression from primary to metastatic melanoma in patients with (V599E)BRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Disease Progression
-
Epitopes / genetics
-
Epitopes / immunology*
-
Epitopes / metabolism
-
Genotype
-
HLA-B Antigens / immunology*
-
HLA-B Antigens / metabolism
-
HLA-B27 Antigen
-
Humans
-
Melanoma / genetics*
-
Melanoma / immunology*
-
Melanoma / secondary
-
Mutation, Missense
-
Peptide Fragments / immunology*
-
Peptide Fragments / metabolism
-
Proto-Oncogene Proteins B-raf
-
Proto-Oncogene Proteins c-raf / genetics*
-
Proto-Oncogene Proteins c-raf / immunology
-
Skin Neoplasms / genetics
-
Skin Neoplasms / immunology
-
Skin Neoplasms / metabolism
-
T-Lymphocytes, Cytotoxic / immunology
-
T-Lymphocytes, Cytotoxic / metabolism
Substances
-
Epitopes
-
HLA-B Antigens
-
HLA-B*27:05 antigen
-
HLA-B27 Antigen
-
Peptide Fragments
-
BRAF protein, human
-
Proto-Oncogene Proteins B-raf
-
Proto-Oncogene Proteins c-raf