Molecular basis of T-cell dysfunction in melanoma

Human melanoma is an immunogenic tumour which is characterized by a number of defined tumour-associated antigens and a specific T-cell-mediated 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 in the tumour- bearing host has become an axiom in tumour immunology. There is increasing evidence that abnormalities in signal transduction events involved in cell activation are the molecular basis for the observed T-cell dysfunction. These abnormalities include altered patterns of protein tyrosin phosphorylation, decreased protein levels of the Src-family kinases p56(lck) and p59(fyn), and of the CD3ζ chain. Furthermore, differences in the expression of transcription factors of the nuclear factor NF-κB/Rel family have been described.