Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125)
Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125)
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DOI：
10.1111/j.1365-2567.2007.02660.x
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发表时间：
2007-11-01
期刊：
影响因子：
6.4
通讯作者：
Patankar, Manish S.
中科院分区：
文献类型：
--
作者：
Belisle, Jennifer A.;Gubbels, Jennifer A. A.;Patankar, Manish S.
卵巢肿瘤标志物MUC16 （CA125）抑制人类自然杀伤（NK）细胞的细胞毒反应，下调CD16。本研究表明，上皮性卵巢癌（EOC）患者外周血NK细胞（PBNK）中约10%为CD16(-) CD56(br)，而40%的腹膜液NK细胞（PFNK）携带这种表型，通常与淋巴结或人蜕膜中的NK细胞有关。暴露于PF的健康供体的PBNK在CD16(-) CD56（br）人群中显着增加。这种表型的转变不是由CD16(+) CD56（dim）细胞的凋亡增加或CD16(-) CD56(br) NK细胞的选择性增殖引起的。因此，在正常NK细胞发育过程中发生的CD16(-) CD56(br) NK细胞向CD16(+) CD56（dim）亚群的最终分化实际上可能是一个可逆的步骤。大多数NK细胞受体（NKp46、NKp44、NKG2D、CD244、CD226、CD158a、CD158b和CD158e）在PFNK中下调。在EOC患者中，MUC16选择性地结合30-40%的CD16(+) CD56(dim) NK细胞，表明这些细胞的表型改变是由肿瘤来源的可溶性因子介导的。与EOC类似，MUC16在妊娠早期也与NK细胞结合，提示NK细胞抑制卵巢癌对胎儿-母体耐受和免疫逃避的共同机制。
The ovarian tumour marker MUC16 (CA125) inhibits the cytotoxic responses of human natural killer (NK) cells and down-regulates CD16. Here we show that approximately 10% of the peripheral blood NK cells (PBNK) from the epithelial ovarian cancer (EOC) patients are CD16(-) CD56(br) whereas 40% of the peritoneal fluid NK (PFNK) carry this phenotype, which is usually associated with NK cells from the lymph nodes or human decidua. PBNK from healthy donors exposed to PF show a significant increase in the CD16(-) CD56(br) population. This shift in phenotype is not caused by increased apoptosis of the CD16(+) CD56(dim) cells or selective proliferation of the CD16(-) CD56(br) NK cells. Thus, the terminal differentiation of the CD16(-) CD56(br) NK cells to CD16(+) CD56(dim) subset that occurs during normal NK cell development may actually be a reversible step. A majority of the NK cell receptors (NKp46, NKp44, NKG2D, CD244, CD226, CD158a, CD158b, and CD158e) studied were down-regulated in the PFNK. MUC16 binds selectively to 30-40% of CD16(+) CD56(dim) NK cells in EOC patients indicating that phenotypic alterations in these cells are mediated by tumour-derived soluble factors. Similar to EOC, MUC16 in early pregnancy also binds to NK cells suggesting shared mechanisms of NK cell suppression in feto-maternal tolerance and immune evasion by ovarian cancers.