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 J Pompili, Hiranmoy Das

Research output: Contribution to journalArticle

21 Citations (Scopus)

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

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Tumor Escape
ovarian neoplasms
T-cells
Tumors
cell cycle
Cell Cycle
T-lymphocytes
Cells
T-Lymphocytes
Molecules
Neoplasms
apoptosis
cyclins
Apoptosis
neoplasm cells
Cyclin D1
Western blotting
Bromodeoxyuridine
pretreatment
immunity

ASJC Scopus subject areas

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

Cite this

Human ovarian tumor cells escape γδ T cell recognition partly by down regulating surface expression of MICA and limiting cell cycle related molecules. / Lu, Jingwei; Aggarwal, Reeva; Kanji, Suman; Das, Manjusri; Joseph, Matthew; Pompili, Vincent J; Das, Hiranmoy.

In: PloS one, Vol. 6, No. 9, e23348, 14.09.2011.

Research output: Contribution to journalArticle

Lu, Jingwei ; Aggarwal, Reeva ; Kanji, Suman ; Das, Manjusri ; Joseph, Matthew ; Pompili, Vincent J ; Das, Hiranmoy. / Human ovarian tumor cells escape γδ T cell recognition partly by down regulating surface expression of MICA and limiting cell cycle related molecules. In: PloS one. 2011 ; Vol. 6, No. 9.
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