CONSTITUTIVE EXPRESSION OF FAS (APO-1 CD95) LIGAND ON MULTIPLE-MYELOMA CELLS - A POTENTIAL MECHANISM OF TUMOR-INDUCED SUPPRESSION OF IMMUNESURVEILLANCE/

The Fas (Apo-1/CD95) ligand (FasL) plays a central role in the elimina tion of target cells by effector T lymphocytes and in the suppression of cellular immune responses against nonmalignant and malignant cells. We show the expression of FasL on the surface of neoplastic plasma ce lls. We provide evidence that the FasL is functionally active because five of five neoplastic plasma cell lines tested killed CEM-C7H2 T-acu te lymphoblastic leukemia (T-ALL) cells. The effect was mediated via t he Fas (Apo-1/CD95) receptor molecule because blocking of Fas on the t arget cells or the FasL on the tumor cells by receptor- and ligand-spe cific monoclonal antibodies (MoAbs), respectively, protected T cells f rom being killed by myeloma cells. In addition, overexpression of the cowpox virus protein CrmA, a molecule with inhibitory potential on cas pase-1 and caspase-8, specifically involved in Fas-induced signaling, protected T cells from being destroyed by the neoplastic cells or the agonistic anti-Fas MoAb, The potential of the malignant plasma cells t o extinguish target T cells was independent of their own sensitivity t o the agonistic anti-Fas MoAb, and FasL-positive (FasL(+)) CEM-C7H2 T cells were incapable of killing myeloma cells, Our results suggest tha t tumor cell-induced suppression of the immune system may be exerted v ia the FasL active on malignant plasma cells. Furthermore, loss of Fas expression or insensitivity to the agonistic anti-Fas MoAb do not see m to be prerequisites for myeloma cells to defeat T cells via Fas/FasL interaction. (C) 1997 by The American Society of Hematology.