EPISIALIN (MUC1) INHIBITS CYTOTOXIC LYMPHOCYTE-TARGET CELL-INTERACTION

Episialin (MUC1) is a mucin-like glycoprotein abundantly expressed on most carcinoma cells. As a result of its extended and rigid structure, it reduces intercellular adhesion. We investigated whether this antia dhesion function allows tumor cells expressing high levels of episiali n to escape from immune recognition. To test this hypothesis, we trans fected episialin-negative (episialin-) melanoma cells (A375) with the MUC1 cDNA-encoding episialin. The results demonstrated that episialin- positive (episialin+) melanoma cells were significantly less susceptib le to lysis than episialin- melanoma cells by both alloantigen or rIL- 2-stimulated cytotoxic effector cells. In addition, cold target inhibi tion experiments with episialin+ and episialin- cells clearly demonstr ated preferential lysis of episialin- cells. Furthermore, antibody blo cking studies showed that lysis of episialin+, but not of episialin-, melanoma cells was predominantly dependent on the leukocyte function-a ssociated Ag-1/intracellular adhesion molecule adhesion route, suggest ing that episialin+ target cells adhere less efficiently to effector c ells than episialin- target cells. This notion was supported by the ob servation that conjugate formation of the effector cells with episiali n+ target cells was significantly impaired. From these results we conc lude that over-expression of episialin as found on many tumor cells ma y indeed affect efficient lysis by cytotoxic lymphocytes and thus may contribute to escape from immune surveillance.