DECREASED EXPRESSION OF SIGNAL-TRANSDUCING ZETA-CHAIN IN PERIPHERAL T-CELLS AND NATURAL-KILLER-CELLS IN PATIENTS WITH CERVICAL-CANCER

An impaired immune response is frequently observed in patients and exp erimental animals with advanced cancer. We and others have shown alter ations in CD3-associated signal-transducing zeta molecules in tumor-in filtrating T cells and peripheral blood lymphocytes (PBLs) of patients with advanced cancer, By using flow cytometric analysis of permeabili zed cells with a monoclonal antibody (TIA-2) that reacts with the cyto plasmic domain of the zeta chain, here we demonstrate a marked decreas e (P < 0.01) in the expression of the signal-transducing CD3 zeta chai n of PBLs in patients with cervical cancer (n = 22) as compared to PBL s from healthy donors (n = 21). In addition, PBLs isolated from patien ts (n = 23) with cervical intraepithelial neoplasia (CIN), to a lesser but significant (P < 0.01) extent, expressed reduced CD3 zeta levels as compared to those from healthy donors, This decreased expression of zeta chains was also observed on CD16(+) natural killer cells in PBLs from patients with cervical cancer, Surface expression of CD3 epsilon on PBLs was also decreased in cervical cancer patients as compared to healthy donors, but not on PBLs from patients with GIN. CD3 zeta chai n expression significantly (r = 0.53, P < 0.01) correlated with the ab ility of the PBLs to produce tumor necrosis factor in response to anti -CD3 stimulation, These findings suggest that alterations of signal-tr ansducing zeta molecules commonly occur in patients with cervical canc er and to a lesser extent with GIN, and that they are associated with reduced cellular functions such as production of tumor necrosis factor .