Sibel Akyol1, Cicek Gercel-Taylor, Lisa C Reynolds, Douglas D Taylor. 1. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Women's Health, University of Louisville School of Medicine, 511 South Floyd Street, MDR 420, Louisville, KY 40292, USA.
Abstract
OBJECTIVE: Suppressed T-cell activation is a hallmark of advanced ovarian cancer. Studies in pregnancy have demonstrated similar T-cell dysfunction mediated, at least in part, by HSP10, identified as "early pregnancy factor." This pilot study addresses the presence of HSP10 in the circulation of ovarian cancer patients and assesses its role in suppressing CD3-zeta. METHODS: Sera were obtained from ovarian cancer patients (n = 10) and age-matched noncancer-bearing female controls (n = 9). HSP10 presence was determined semiquantitatively by Western immunoblotting in sera, ascites, and ovarian tumor cell conditioned media. The consequences of HSP10 on CD3-zeta suppression were defined using a Jurkat cell bioassay, using unfractionated patient sera, sera with HSP10 removed by immunoprecipitation and the immunoprecipitate. RESULTS: HSP10 was detected in both sera and ascites of patients with ovarian cancer; however, it was not detectable in controls. HSP10 was also detected in the culture media of ovarian tumor cells. Sera containing HSP10 suppressed T-cell CD3-zeta expression, which correlated with HSP10 levels (r2 = 0.839). When HSP10 was removed from the sera, the ability to suppress CD3-zeta was diminished and the immunoprecipitated material was capable of suppressing CD3-zeta. CONCLUSIONS: HSP10 appears to be produced and released from ovarian tumor cells and is detectable in the peripheral blood and ascites of patients. This circulating HSP10 appears to suppress T-cell expression of CD3-zeta, a key component of T-cell activation. Our findings indicate that, as in pregnancy, production and release of HSP10 may be a critical factor in the suppression of T-cell activation, allowing the tumor to escape immune surveillance.
OBJECTIVE: Suppressed T-cell activation is a hallmark of advanced ovarian cancer. Studies in pregnancy have demonstrated similar T-cell dysfunction mediated, at least in part, by HSP10, identified as "early pregnancy factor." This pilot study addresses the presence of HSP10 in the circulation of ovarian cancerpatients and assesses its role in suppressing CD3-zeta. METHODS: Sera were obtained from ovarian cancerpatients (n = 10) and age-matched noncancer-bearing female controls (n = 9). HSP10 presence was determined semiquantitatively by Western immunoblotting in sera, ascites, and ovarian tumor cell conditioned media. The consequences of HSP10 on CD3-zeta suppression were defined using a Jurkat cell bioassay, using unfractionated patient sera, sera with HSP10 removed by immunoprecipitation and the immunoprecipitate. RESULTS:HSP10 was detected in both sera and ascites of patients with ovarian cancer; however, it was not detectable in controls. HSP10 was also detected in the culture media of ovarian tumor cells. Sera containing HSP10 suppressed T-cell CD3-zeta expression, which correlated with HSP10 levels (r2 = 0.839). When HSP10 was removed from the sera, the ability to suppress CD3-zeta was diminished and the immunoprecipitated material was capable of suppressing CD3-zeta. CONCLUSIONS:HSP10 appears to be produced and released from ovarian tumor cells and is detectable in the peripheral blood and ascites of patients. This circulating HSP10 appears to suppress T-cell expression of CD3-zeta, a key component of T-cell activation. Our findings indicate that, as in pregnancy, production and release of HSP10 may be a critical factor in the suppression of T-cell activation, allowing the tumor to escape immune surveillance.
Authors: Gayathri T Selvarajah; Floor A S Bonestroo; Jolle Kirpensteijn; Marja J L Kik; Ruurd van der Zee; Willem van Eden; Elpetra P M Timmermans-Sprang; Adri Slob; Jan A Mol Journal: Cell Stress Chaperones Date: 2013-03-06 Impact factor: 3.667
Authors: G Tomasello; C Sciumé; F Rappa; V Rodolico; M Zerilli; A Martorana; G Cicero; R De Luca; P Damiani; F M Accardo; M Romeo; F Farina; G Bonaventura; G Modica; G Zummo; E Conway de Macario; A J L Macario; F Cappello Journal: Eur J Histochem Date: 2011-10-24 Impact factor: 3.188