title: Human ovarian tumor cells escape γδ T cell recognition partly by down regulating surface expression of MICA and limiting cell cycle related molecules.
abstract: BACKGROUND
  Mechanisms of human Vγ2Vδ2 T cell-mediated tumor immunity have yet to be fully elucidated.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings demonstrate novel effects of γδT cells on ovarian tumor cells.
authors.affiliation: Cardiovascular Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Lu
authors.forename: Reeva
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Suman
authors.initials: S
authors.lastname: Kanji
authors.forename: Manjusri
authors.initials: M
authors.lastname: Das
authors.forename: Matthew
authors.initials: M
authors.lastname: Joseph
authors.forename: Vincent
authors.initials: V
authors.lastname: Pompili
authors.forename: Hiranmoy
authors.initials: H
authors.lastname: Das
mesh_terms: D017209:Apoptosis; D002450:Cell Communication; D002453:Cell Cycle; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3