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


ABSTRACT:

Background

Mechanisms of human V?2V?2 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 V?2V?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. ?? T cell-resistant, but not susceptible ovarian tumor cells escape ?? 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 ?? T cell-mediated lysis.

Conclusion

These findings demonstrate novel effects of ??T cells on ovarian tumor cells.

SUBMITTER: Lu J 

PROVIDER: S-EPMC3173356 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

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 J   Aggarwal Reeva R   Kanji Suman S   Das Manjusri M   Joseph Matthew M   Pompili Vincent V   Das Hiranmoy H  

PloS one 20110914 9


<h4>Background</h4>Mechanisms of human Vγ2Vδ2 T cell-mediated tumor immunity have yet to be fully elucidated.<h4>Methods and findings</h4>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-resist  ...[more]

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