UV-induced N-ras mutations are T-cell targets in human melanoma.
Human cutaneous melanoma is heterogeneous with respect to the genetic aberrations involved and the genes altered are potential targets for the immune system. The incidence of cutaneous melanoma is known to be linked to UV peak exposure, and the N-ras oncogene is clearly one of the genes involved in the UV carcinogenesis in melanoma. It is mutated in a significant proportion of melanomas and therefore may serve as a target for T cells. Here, we report that an human leukocyte antigen-A2 binding peptide CLLDILDTAGL, encompassing the frequently found 61-Leu mutation in N-ras, induces cytotoxic T lymphocytes from healthy donor blood that lyse 61-Leu N-ras transfected melanoma cells. Furthermore, we have found an association between the presence of N-ras mutations and clinical response to immunotherapy with interleukin-2 plus interferon in a group of stage IV melanoma patients. Although the overall survival of these patients was not affected by the N-ras status of their melanomas, these studies suggest that mutated N-ras may provide a target for cytotoxic T lymphocytes in melanoma patients.
van Elsas
A
A
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
Scheibenbogen
C
C
van der Minne
C
C
Zerp
S F
SF
Keilholz
U
U
Schrier
P I
PI
D000328:Adult; D000368:Aged; D005260:Female; D011905:Genes, ras / Q000528:radiation effects*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D009154:Mutation; D012878:Skin Neoplasms / Q000235:genetics* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D018631:ras Proteins / Q000235:genetics* / Q000276:immunology* / Q000528:radiation effects
D018631:ras Proteins