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
Department of Clinical Therapeutics, University of Athens, Greece.
Gynecol Oncol. 2007 Jul;106(1):75-81. doi: 10.1016/j.ygyno.2007.02.029. Epub 2007 Apr 11.
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.
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.
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.
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.
肿瘤浸润淋巴细胞(TILs)和调节性T细胞(Tregs)与卵巢癌预后相关,但其在腹水中的预后意义尚未得到研究。我们对从卵巢癌患者腹水中分离出的T淋巴细胞进行了一项前瞻性研究,并将其与血液和肿瘤中的相应细胞群进行比较。
通过Ficoll分离腹水(n = 71)和血液中的单核细胞,通过机械解离获得肿瘤淋巴细胞(n = 20)。采用流式细胞术进行表型分析。将10例肝硬化患者的腹水用作对照。
与血液和对照腹水相比,肿瘤腹水中含CD4(+)CD25(+)细胞的Tregs、含CD3(+)CD56(+)细胞的NK-T以及CD4和CD8淋巴细胞的CD69和HLADR表达显著增加。癌症患者腹水中这些细胞群的选择性积聚表现为其腹水/血液(A/B)比值显著高于对照组。腹水中癌细胞含量与CD4(+)CD25(+)、CD4(+)CD69(+)、CD4(+)HLADR(+)和CD8(+)CD69(+)细胞相关。腹水与腹膜转移样本中的淋巴细胞群之间无相关性。较高的肿瘤分级与A/B CD4(+)CD25(+)比值增加及CD3(+)CD56(+)细胞减少相关,而铂耐药与A/B CD3(+)CD56(+)比值降低相关。
卵巢癌患者血液、腹水和腹膜转移灶之间,CD3(+)CD56(+)和CD25(+)CD4(+)淋巴细胞存在显著差异且淋巴细胞活化增加。腹水中CD3(+)CD56(+)细胞群的选择性积聚可能是铂耐药的预测因素。