Selective expression of FLIP in malignant melanocytic skin lesions

FLIP (FLICE Inhibitory Protein) is a recently identified intracellular inhi bitor of caspase-8 activation that potently inhibits cell death mediated by all death receptors including Fas and TRAIL. FLIP has recently been shown to favor tumor growth and immune escape in mouse tumor models. We analyzed FLIP expression by immunohistochemistry in a panel of 61 benign and maligna nt human melanocytic skin lesions. FLIP expression was undetectable in all but one benign melanocytic lesion (31/32, 97%). In contrast, FLIP was stron gly expressed in most melanomas (24/29 = 83%). Overexpression of FLIP by tr ansfection in a Fas- and TRAIL-sensitive human melanoma cell line rendered thus cell line more resistant to death mediated by both TR ATL and FasL. Se lective expression of FLIP by human melanomas may confer ht vivo resistance to FasL and TRAIL, thus representing an additional mechanism by which mela noma cells escape immune destruction.