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.

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.