Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+ CD56+ cells with platinum resistance

• Published in: Gynecologic oncology 2007-07, Vol.106 (1), p.75-81
• Main Authors: Bamias, A, Tsiatas, M.L, Kafantari, E, Liakou, C, Rodolakis, A, Voulgaris, Z, Vlahos, G, Papageorgiou, T, Tsitsilonis, O, Bamia, C, Papatheodoridis, G, Politi, Ek, Archimandritis, A, Antsaklis, A, Dimopoulos, M.A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Ascites - immunology; Ascites - pathology; CD3 Complex - biosynthesis; CD3 Complex - immunology; CD56 Antigen - biosynthesis; CD56 Antigen - immunology; Drug Resistance, Neoplasm; Female; Flow Cytometry; Hematology, Oncology and Palliative Medicine; Humans; Immune response; Interleukin-2 Receptor alpha Subunit - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Middle Aged; Neoplasm Staging; NK-T; Obstetrics and Gynecology; Organoplatinum Compounds - pharmacology; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Tregs
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2007.02.029

Abstract Objectives Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T lymphocytes isolated from ascites from patients with ovarian carcinoma and we compared them with the respective populations in blood and tumors. Methods Mononuclear cells from ascites ( n = 71) and blood were isolated by Ficoll, while tumor lymphocytes ( n = 20) were obtained upon mechanical dissociation. Phenotypic analysis was performed with flow cytometry. Ascites from 10 patients with cirrhosis was used as control. Results Tregs containing CD4+ CD25+ cells, NK-T containing CD3+ CD56+ cells and CD69 and HLADR expression of CD4 and CD8 lymphocytes were significantly increased in tumor ascites compared to blood and control ascites. A selective accumulation of these populations in the ascites of cancer patients, was suggested by the significantly higher ascites/blood (A/B) ratios in cancer patients but not controls. Cancer cell content in ascites was correlated with CD4+ CD25+ , CD4+ CD69+ , CD4+ HLADR+ and CD8+ CD69+ cells. There was no correlation of lymphocyte populations between ascites and samples from peritoneal metastases. Higher tumor grade was associated with increased A/B CD4+ CD25+ ratio and reduced CD3+ CD56+ cells, while platinum resistance was associated with reduced A/B CD3+ CD56+ ratio. Conclusions There are significant differences of CD3+ CD56+ and CD25+ CD4+ lymphocytes and increase in lymphocyte activation between blood, ascites and peritoneal metastases from patients with ovarian cancer. The selective accumulation of CD3+ CD56+ population in ascites may be a predictive factor for platinum resistance.