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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Sep 22

PMID 21935360

Citations 15

Authors

Jingwei Lu

Reeva Aggarwal

Suman Kanji

Manjusri Das

Matthew Joseph

Vincent Pompili

Hiranmoy Das

Affiliations

Soon will be listed here.

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.

Citing Articles

Ovarian cancer stem cells: Critical roles in anti-tumor immunity.

Ding J, Zhang Y, Che Y Front Genet. 2022; 13:998220.

PMID: 36437919 PMC: 9685611. DOI: 10.3389/fgene.2022.998220.

The Dual Roles of Human γδ T Cells: Anti-Tumor or Tumor-Promoting.

Li Y, Li G, Zhang J, Wu X, Chen X Front Immunol. 2021; 11:619954.

PMID: 33664732 PMC: 7921733. DOI: 10.3389/fimmu.2020.619954.

Diversity of Tumor-Infiltrating, γδ T-Cell Abundance in Solid Cancers.

Chabab G, Boissiere-Michot F, Mollevi C, Ramos J, Lopez-Crapez E, Colombo P Cells. 2020; 9(6).

PMID: 32599843 PMC: 7348937. DOI: 10.3390/cells9061537.

Distribution and functions of γδ T cells infiltrated in the ovarian cancer microenvironment.

Chen X, Shang W, Xu R, Wu M, Zhang X, Huang P J Transl Med. 2019; 17(1):144.

PMID: 31064389 PMC: 6505080. DOI: 10.1186/s12967-019-1897-0.

Functional Plasticity of Gamma Delta T Cells and Breast Tumor Targets in Hypoxia.

Siegers G, Dutta I, Lai R, Postovit L Front Immunol. 2018; 9:1367.

PMID: 29963058 PMC: 6013583. DOI: 10.3389/fimmu.2018.01367.

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