Human Ovarian Tumor Cells Escape [gamma][delta] T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules

• Published in: PloS one Vol. 6; no. 9; p. e23348
• Main Authors: Lu, Jingwei, Aggarwal, Reeva, Kanji, Suman, Das, Manjusri, Joseph, Matthew, Pompili, Vincent, Das, Hiranmoy
• Format: Journal Article
• Language: English
• Published: Public Library of Science 14.09.2011
• Subjects: Apoptosis; Cell cycle; Ovarian cancer; T cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023348

Mechanisms of human V[gamma]2V[delta]2 T cell-mediated tumor immunity have yet to be fully elucidated. 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 V[gamma]2V[delta]2 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. [gamma][delta] T cell-resistant, but not susceptible ovarian tumor cells escape [gamma][delta] 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 [gamma][delta] T cell-mediated lysis. These findings demonstrate novel effects of [gamma][delta]T cells on ovarian tumor cells.