human ovarian tumor cells escape γδ t cell recognition partly by down regulating surface expression of mica and limiting cell cycle related molecules人类卵巢肿瘤细胞逃避γδt细胞识别部分通过调节表面表达的云母和限制细胞周期相关的分子.pdfVIP

Human Ovarian Tumor Cells Escape cd T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules 1 1 1 1 1 1 Jingwei Lu , Reeva Aggarwal , Suman Kanji , Manjusri Das , Matthew Joseph , Vincent Pompili , Hiranmoy Das1,2* 1 Cardiovascular Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America, 2 Innate Immunity, Comprehensive Cancer Center, Richard J. Solove Research Institute, Arthur G. James Cancer Hospital, The Ohio State University, Columbus, Ohio, United States of America Abstract Background: Mechanisms of human Vc2Vd2 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 Vc2Vd2 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. cd T cell-resistant, but not susceptible ovarian tumor cells escape cd 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 cd T cell-mediated lysis. Conclusion: These findings demonstrate novel effects of cdT cells on ovarian tumor cells. Citation: Lu J, Aggarwal R, Kanji S, Das M, Joseph M, et al. (2011) Human Ovarian Tumor Cells Escape cd T Cell