人卵巢肿瘤细胞通过下调表面 MICA 的表达和限制细胞周期相关分子来部分逃避 γδ T 细胞的识别。

Human ovarian tumor cells escape γδ T cell recognition partly by down regulating surface expression of MICA and limiting cell cycle related molecules.

机构信息

Cardiovascular Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.

出版信息

PLoS One. 2011;6(9):e23348. doi: 10.1371/journal.pone.0023348. Epub 2011 Sep 14.

BACKGROUND

Mechanisms of human Vγ2Vδ2 T cell-mediated tumor immunity have yet to be fully elucidated.

METHODS AND FINDINGS

At least some tumor cell recognition is mediated by NKG2D-MICA interactions. Herein, by using MTT assay and PI-BrdU co-staining and Western-blot, we show that these Vγ2Vδ2 T cells can limit the proliferation of ovarian tumor cells by down regulation of apoptosis and cell cycle related molecules in tumor cells. Cell-to-cell contact is critical. γδ T cell-resistant, but not susceptible ovarian tumor cells escape γδ T cell-mediated immune recognition by up-regulating pErk1/2, thereby decreasing surface MICA levels. Erk1/2 inhibitor pretreatment or incubation prevents this MICA decrease, while up-regulating key cell cycle related molecules such as CDK2, CDK4 and Cyclin D1, as well as apoptosis related molecules making resistant tumor cells now vulnerable to γδ T cell-mediated lysis.

CONCLUSION

These findings demonstrate novel effects of γδT cells on ovarian tumor cells.

背景

人类 Vγ2Vδ2 T 细胞介导的肿瘤免疫的机制尚未完全阐明。

方法和发现

至少有一些肿瘤细胞的识别是由 NKG2D-MICA 相互作用介导的。在此，通过 MTT 检测、PI-BrdU 共染色和 Western blot，我们表明这些 Vγ2Vδ2 T 细胞可以通过下调肿瘤细胞中凋亡和细胞周期相关分子来限制卵巢肿瘤细胞的增殖。细胞间接触是关键的。γδ T 细胞耐药但不易感的卵巢肿瘤细胞通过上调 pErk1/2 逃避 γδ T 细胞介导的免疫识别，从而降低表面 MICA 水平。Erk1/2 抑制剂预处理或孵育可防止这种 MICA 减少，同时上调关键细胞周期相关分子，如 CDK2、CDK4 和 Cyclin D1，以及凋亡相关分子，使耐药肿瘤细胞现在易受 γδ T 细胞介导的裂解。