Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in squamous-cell carcinoma by interferon-gamma and cisplatin

CD95 (Apo-I/Fas) ligand (CD95L) expression has been observed in various mal ignancies. In human primary cell lines from a squamous cell carcinoma (SCC) of the vulva, the effect of cisplatin (CDDP) and IFN gamma on the expressi on of CD95L and its 2 receptor isoforms, CD95 transmembrane (CD95tm) and CD 95 soluble receptor, was studied at the mRNA and protein levels. Addition o f CDDP and IFN gamma increased CD95L mRNA levels in the primary cell line 6 -fold and 1.7-fold, respectively, In comparison, CD95tm mRNA levels were di minished by CDDP but increased 8-fold upon IFN gamma challenge, CD95L expre ssed by SCC cells was functionally relevant since these cells were able to induce CD95-specific apoptosis in autologous lymphocytes from the SCC-beari ng patient. Thus, CD95L expression in SCC may contribute to tumor-associate d immunosuppression, which may be modulated by CDDP and IFN gamma. In tumor samples of the primary SCC, CD95L expression was enhanced in the area of t he border between invasive tumor tissue and surrounding stroma cells, The l ocally restricted over-expression of CD95L was congruent with the arrangeme nt of apoptotic stroma cells in the direct vicinity of invading tumor tongu es, suggesting a role as invasion factor for CD95L. (C) 1999 Wiley-Liss, In c.