Human ovarian cancer stem-like cells can be efficiently killed by γδ T lymphocytes

Cancer Immunol Immunother. 2012 Jul;61(7):979-89. doi: 10.1007/s00262-011-1166-4. Epub 2011 Nov 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • G2 Phase Cell Cycle Checkpoints / immunology
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • M Phase Cell Cycle Checkpoints / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / immunology
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / therapy*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays


  • HLA-DR Antigens
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta