Immunogenicity of constitutively active V599EBRaf.
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.
Insitute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Mads Hald
MH
Andersen
Joachim
J
Fensterle
Selma
S
Ugurel
Sine
S
Reker
Roland
R
Houben
Per
P
Guldberg
Thomas G
TG
Berger
Dirk
D
Schadendorf
Uwe
U
Trefzer
Eva-B
EB
Bröcker
Per thor
Pt
Straten
Ulf R
UR
Rapp
Jürgen C
JC
Becker
D018450:Disease Progression; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005838:Genotype; D015235:HLA-B Antigens / Q000276:immunology* / Q000378:metabolism; D015796:HLA-B27 Antigen; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000556:secondary; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015235:HLA-B Antigens; C464936:HLA-B*27:05 antigen; D015796:HLA-B27 Antigen; D010446:Peptide Fragments; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf