HUMAN INTERLEUKIN FOR DA CELLS LEUKEMIA INHIBITORY FACTOR AND ONCOSTATIN-M ENHANCE MEMBRANE EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1ON MELANOMA-CELLS BUT NOT THE SHEDDING OF ITS SOLUBLE FORM

ICAM-1-mediated cell-cell adhesion is essential for different immunolo gic functions including non-MHC-restricted cytotoxicity. The shedding of a soluble form of ICAM-1 from melanoma impairs immune recognition a nd leads to tumour escape, Pretreatment of the Foss human melanoma cel l line with HILDA/LIF or OSM, two cytokines involved in acute-phase re sponse, increased the expression of membrane ICAM-1 twofold without in ducing sICAM-1 shedding, Conversely, TNF-alpha, in the same conditions , strongly stimulated membrane ICAM-1 expression and the shedding of t he soluble form, The same phenomenon was observed on the A375 human me lanoma cell line, ICAM-1 upregulation was concomitant with an increase in the non-MHC-restricted cytotoxicity of tumour cells mediated by LA K cells, This higher sensitivity to LAK lysis was abolished by RR1/1, a specific monoclonal antibody against ICAM-1, Our results demonstrate for the first time the ability of HILDA/LIF and OSM to upregulate ICA M-1 expression on the melanoma cell surface, suggesting a potential ro le for these cytokines in human immune surveillance during tumour prog ression.