Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines derived from the same patient

Progressive tumor growth may be associated with suppression of the immune r esponse. Many different mechanisms may contribute to immune evasion. We inv estigated some of these mechanisms in melanoma cells lines generated from t wo patients. These cell lines show a complex pattern of altered HLA express ion; however, the resulting phenotype did not satisfactorily explain the si multaneous evasion of T and NK cell cytotoxicity. Two additional alteration s have now been detected in these melanoma cell lines: (1) resistance to FA S-induced apoptosis caused by defective FAS gene expression, and (2) consti tutive expression of immunosuppressive cytokines. Our results show that sev eral of the major mechanisms for immune evasion may coexist in a single tum or. This suggests that tumor progression may give rise to an extremely resi stant phenotype, which may be an impediment to some immunotherapeutic strat egies. We hypothesize that the simultaneous presence of several mechanisms involved in tumor immune evasion must be the result of progressive selectio n of characteristics that are advantageous for tumor survival in a competen t host. Our findings do not support the possibility that FASL expression is a common mechanism of evasion of immune response in melanoma cells.