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 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.
| Original language | English |
|---|---|
| Journal | Cancer Research |
| Volume | 64 |
| Issue number | 15 |
| Pages (from-to) | 5456-5460 |
| Number of pages | 5 |
| ISSN | 0008-5472 |
| DOIs | |
| Publication status | Published - 2004 |
| Externally published | Yes |
Keywords
- Cancer Research
- Oncology
- B Raf kinase
- epitope
- gene product
- glutamic acid
- HLA B antigen
- mutant protein
- unclassified drug
- valine
- amino acid substitution
- antigen recognition
- article
- braf gene
- cell clone
- cell selection
- cellular immunity
- clonal selection
- controlled study
- cytotoxic T lymphocyte
- gene
- genotype
- host
- human
- human cell
- immunogenicity
- immunoselection
- major histocompatibility complex restriction
- melanoma
- melanoma cell
- metastasis
- missense mutation
- priority journal
- somatic mutation
- tumor bearing host
- tumor growth
- wild type
- Disease Progression
- Epitopes
- Genotype
- HLA-B Antigens
- Humans
- Melanoma
- Mutation, Missense
- Peptide Fragments
- Proto-Oncogene Proteins B-raf
- Proto-Oncogene Proteins c-raf
- Skin Neoplasms
- T-Lymphocytes, Cytotoxic
