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

Jingwei Lu, Reeva Aggarwal, Suman Kanji, Manjusri Das, Matthew Joseph, Vincent Pompili, Hiranmoy Das

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere23348
JournalPloS one
Volume6
Issue number9
DOIs
StatePublished - Sep 14 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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