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.
OBJECTIVE
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.
Bamias
A
A
Department of Clinical Therapeutics, University of Athens, Greece. abamias@med.uoa.gr <abamias@med.uoa.gr>
Tsiatas
M L
ML
Kafantari
E
E
Liakou
C
C
Rodolakis
A
A
Voulgaris
Z
Z
Vlahos
G
G
Papageorgiou
T
T
Tsitsilonis
O
O
Bamia
C
C
Papatheodoridis
G
G
Politi
Ek
E
Archimandritis
A
A
Antsaklis
A
A
Dimopoulos
M A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology*; D019002:CD56 Antigen / Q000096:biosynthesis / Q000276:immunology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D017252:CD3 Complex; D019002:CD56 Antigen; D053645:Interleukin-2 Receptor alpha Subunit; D009944:Organoplatinum Compounds