title: Human ovarian cancer stem-like cells can be efficiently killed by γδ T lymphocytes.
abstract: Ovarian cancer comprises a small population of cancer stem cells (CSCs) that are responsible for tumor maintenance and resistant to cancer therapies, it would be desirable to develop a therapy that could selectively target ovarian CSCs. Recently, cellular immune-based therapies have improved the prognosis of cancer patients clinically. In this study, we isolated a subset of ovarian cancer sphere cells that possess CSC properties and explored the cell cytotoxicity of γδ T cells to ovarian cancer sphere cells using a transwell cocultured cell system. The proliferation rate of the cancer sphere cells decreased to 40% after cocultured with γδ T cells. The γδ T cells increased the sensitivity of SK-OV-3 sphere cells to chemotherapeutic drugs. After the treatment of γδ T cells, the expression of stem cell marker genes decreased in sphere cells, while the expression of HLA-DR antigen on tumor cells was increased in a time-dependent manner. Further, γδ T cells induced G2/M phase cell cycle arrest and subsequent apoptosis in SK-OV-3 sphere cells. Xenograft mouse models demonstrated that γδ T cells dramatically reduced the tumor burden. Notably, the level of IL-17 production significantly increased after cocultured with γδ T cells. We conclude that γδ T cells may efficiently kill ovarian CSCs through IL-17 production and represent a promising immunotherapy for ovarian cancer.
authors: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, China. laidongmei@hotmail.com
authors: Dongmei
authors: D
authors: Lai
authors: Fangyuan
authors: F
authors: Wang
authors: Yifei
authors: Y
authors: Chen
authors: Chunhui
authors: C
authors: Wang
authors: Sha
authors: S
authors: Liu
authors: Bufeng
authors: B
authors: Lu
authors: Xirui
authors: X
authors: Ge
authors: Lihe
authors: L
authors: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D059566:M Phase Cell Cycle Checkpoints / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D006684:HLA-DR Antigens; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta