FAVORABLE MELANOMA PROGNOSIS ASSOCIATED WITH THE EXPRESSION OF THE TUMOR-NECROSIS-FACTOR RECEPTOR AND THE ALPHA(1)BETA(1) INTEGRIN - A PRELIMINARY-REPORT

Recently we encountered a patient (p1) with a Clark's level IV melanom a associated with recurrent cutaneous metastasis who subsequently expe rienced a complete remission after a period of therapy with dichloroni trobenzene (DCNB) and interferon-alpha (IFN alpha). Another patient (p 2) with a similar Clark's level of disease but with a fatal prognosis and melanoma cells from the Sk-Mel 28 and MeWo cell lines served as co ntrol groups. Since cytokines and members of the alpha(1) integrin fam ily have been implicated in the growth and metastatic behaviour of mel anomas, we evaluated the cytokine effects and integrins expressed by m elanoma cells in the patients' tumours. P1, but not p2 nor MeWo melano ma cells, expressed HLA-DR, alpha(1) beta(1) and the tumour necrosis f actor receptor (TNF-R). Culturing p1 melanoma cells with TNF alpha, bu t not MeWo or p2 melanoma cells, increased their expression of alpha(1 ) beta(1) integrin and was cytotoxic for the cells. Significant in viv o growth of metastatic p1 and p2 melanoma explants as well as MeWo cel ls grafted subcutaneously onto nude mice was noted over 36 days. Intra lesional injection of TNF alpha induced complete regression of p1 expl ants, but not of p2 or MeWo explants. Intralesional injection of IFN a lpha or anti-alpha(1) beta(1) integrin arrested p1 graft growth. These results suggest that the slow growth of the melanoma cells in nude mi ce, as well as the susceptibility to tumour killing by TNF alpha and t he dependence of the tumour on signals mediated by the alpha(1) beta(1 ) integrin are features that may have contributed to the beneficial th erapeutic response in patient 1.