Landskron Johannes, Helland Øystein, Torgersen Knut Martin, Aandahl Einar Martin, Gjertsen Bjørn Tore, Bjørge Line, Taskén Kjetil
Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
Cancer Immunol Immunother. 2015 Mar;64(3):337-47. doi: 10.1007/s00262-014-1636-6. Epub 2014 Nov 22.
Invasive ovarian cancer is associated with poor outcome. The presence of infiltrating regulatory T-cells (Tregs) suppresses protective anti-tumor immune responses, and their accumulation into the tumor microenvironment correlates with reduced survival in ovarian cancer patients. Here, we conducted a detailed characterization of CD4(+) T-cells, CD8(+) T-cells and Treg subsets in the peripheral blood and malignant ascites fluid from seventeen patients with ovarian carcinoma of epithelial origin. Cell distribution, activation status and proliferation status were assessed by multi-color flow cytometry. In ascites fluid, a significant accumulation of CD8(+) cytotoxic T-cells and Tregs was observed compared to peripheral blood. Furthermore, a skewing toward the CD45RA(-) effector/memory compartment was observed in all T-cell subsets in the ascites fluid, but was most pronounced in the Treg population. Regulatory T-cells in the malignant ascites were more activated and had a higher proliferation rate compared to blood-derived cells from the same patient, and their number in ascites was positively correlated with the number of epithelial cells in effusion. In summary, we demonstrate an accumulation of activated CD4(+), CD8(+) and regulatory T-cells in the cancer microenvironment of ovarian carcinoma.
侵袭性卵巢癌预后较差。浸润性调节性T细胞(Tregs)的存在会抑制保护性抗肿瘤免疫反应,它们在肿瘤微环境中的积累与卵巢癌患者生存率降低相关。在此,我们对17例上皮性卵巢癌患者外周血和恶性腹水中的CD4(+) T细胞、CD8(+) T细胞和Treg亚群进行了详细表征。通过多色流式细胞术评估细胞分布、活化状态和增殖状态。与外周血相比,腹水中观察到CD8(+) 细胞毒性T细胞和Tregs显著积聚。此外,腹水中所有T细胞亚群均呈现向CD45RA(-) 效应/记忆亚群的偏移,在Treg群体中最为明显。与同一患者的血液来源细胞相比,恶性腹水中的调节性T细胞更具活化性且增殖率更高,腹水中其数量与积液中上皮细胞数量呈正相关。总之,我们证明了卵巢癌癌微环境中活化的CD4(+)、CD8(+) 和调节性T细胞的积聚。