Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients

In women with ovarian cancer, suppression of components of the immune syste m may promote tumour development. Previous studies in ovarian cancer have d emonstrated that decreased expression and function of the T-cell receptor ( TcR)-associated signal transducing zeta-chain correlates with deficient imm une responsiveness of T cells. In this study, sera and ascitic fluids obtai ned from woman with advanced ovarian cancer were found to suppress the expr ession of TcR-associated zeta chain. This suppression of zeta chain express ion was dose-dependent and was not observed with biologic fluids obtained f rom healthy women. The factor responsible for the loss: of zeta chain was purified from ascite s and characterized as a protein with an appropriate molecular weight of 14 kD. Suppression of T-cell TcR-zeta was specific, since neither lck nor ZAP -70 expression was affected, while zeta chain was almost completely suppres sed. This selective suppression of TcR-zeta expression by the 14 kD ascites -derived factor was shown to operate at the mRNA level. By defining the mec hanism through which this protein modulates TcR-zeta chain levels, it might be possible to ultimately prevent the suppressive influences of the tumour microenvironment and rester immune competence in patients with ovarian car cinoma. (C) 2001 Cancer Research Campaign.