title: Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients.
abstract: In women with ovarian cancer, suppression of components of the immune system may promote tumour development. Previous studies in ovarian cancer have demonstrated that decreased expression and function of the T-cell receptor (TcR)-associated signal transducing zeta-chain correlates with deficient immune responsiveness of T cells. In this study, sera and ascitic fluids obtained from woman with advanced ovarian cancer were found to suppress the expression of TcR-associated zeta chain. This suppression of zeta chain expression was dose-dependent and was not observed with biologic fluids obtained from healthy women. The factor responsible for the loss of zeta chain was purified from ascites 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 suppressed. 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 mechanism through which this protein modulates TcR-zeta chain levels, it might be possible to ultimately prevent the suppressive influences of the tumour microenvironment and restor immune competence in patients with ovarian carcinoma.
authors.affiliation: Department of Obstetrics, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Taylor
authors.forename: D P
authors.initials: DP
authors.lastname: Bender
authors.lastname: Gerçel-Taylor C
authors.forename: J
authors.initials: J
authors.lastname: Stanson
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000328:Adult; D001201:Ascites; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007121:Immunocompetence; D007165:Immunosuppression Therapy; D008565:Membrane Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain