IL2 TRIGGERS A TUMOR PROGRESSION PROCESS IN A MELANOMA CELL-LINE MELP, DERIVED FROM A PATIENT WHOSE METASTASIS INCREASED IN SIZE DURING IL2INF-ALPHA BIOTHERAPY/

Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may gen erate biological situations which may be favourable for the patient, b ut also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2 / IFN alpha. biotheraphy. These cells hav e been characterized in vitro for their phenotype and for their sensit ivity to IL2. In vitro MELP cells express an IL2-R alpha(+)beta(+)gamm a(-) phenotype and IL2 treatment induces the acquisition of new functi onal characteristics represented (i) by the increased surface expressi on of two markers of metastatic evolution (ICAM-1 and by the stable CD 44); (ii) induction of the IL2-R gamma, with the appearance of functio nal IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MEL P cells treated or not with IL2 (MILG cells); (v) by the acquisition o f faster growth rates and appearance of piling up and multilayer cellu lar organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biothera py. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.