MOLECULAR-BASIS OF T-CELL DYSFUNCTION IN MELANOMA

Human melanoma is an immunogenic tumour which is characterized by a nu mber of defined tumour-associated antigens and a specific T-cell-media ted immune response. Nevertheless, there is only limited evidence for an effective antitumour immune response able to eradicate established melanoma. Thus, the existence of an immunologically suppressed state i n the tumour-bearing host has become an axiom in tumour immunology. Th ere is increasing evidence that abnormalities in signal transduction e vents involved in cell activation are the molecular basis for the obse rved T-cell dysfunction. These abnormalities include altered patterns of protein tyrosin phosphorylation, decreased protein levels of the Sr c-family kinases p56(lck) and p59(fyn), and of the CD3 zeta chain. Fur thermore, differences in the expression of transcription factors of th e nuclear factor NF-kappa B/Rel family have been described.