Ex vivo-expanded NK cells from blood and ascites of ovarian cancer patients are cytotoxic against autologous primary ovarian cancer cells

Cancer Immunol Immunother. 2018 Apr;67(4):575-587. doi: 10.1007/s00262-017-2112-x. Epub 2018 Jan 3.


Ovarian cancer (OC) is the leading cause of gynecological cancer-related death in North America. Most ovarian cancer patients (OCPs) experience disease recurrence after first-line surgery and chemotherapy; thus, there is a need for novel second-line treatments to improve the prognosis of OC. Although peripheral blood-derived NK cells are known for their ability to spontaneously lyse tumour cells without prior sensitization, ascites-derived NK cells (ascites-NK cells) isolated from OCPs exhibit inhibitory phenotypes, impaired cytotoxicity and may play a pro-tumourigenic role in cancer progression. Therefore, it is of interest to improve the cytotoxic effector function of impaired OCP ascites-NK cells at the tumour environment. We investigated the efficacy of using an artificial APC-based ex vivo expansion technique to generate cytotoxic, expanded NK cells from previously impaired OCP ascites-NK cells, for use in an autologous model of NK cell immunotherapy. We are the first to obtain a log-scale expansion of OCP ascites-NK cells that upregulate the surface expression of activating receptors NKG2D, NKp30, NKp44, produce robust amounts of anti-tumour cytokines in the presence of OC cells and mediate direct tumour cytotoxicity against ascites-derived, primary OC cells obtained from autologous patients. Our findings demonstrate that it is possible to generate cytotoxic OCP ascites-NK cells from previously impaired OCP ascites-NK cells, which presents a promising immunotherapeutic target for the second-line treatment of OC. Future work should focus on evaluating the in vivo efficacy of autologous NK cell immunotherapy through the intraperitoneal delivery of NK cell expansion factors to a preclinical xenograft mouse model of human OC.

Keywords: Ascites; Autologous natural killer cells; Ex vivo NK cell expansion; Natural killer cell cancer immunotherapy; Ovarian cancer.

MeSH terms

  • Ascites / immunology*
  • Ascites / metabolism
  • Cell Proliferation
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / immunology*
  • Female
  • Humans
  • Immunotherapy*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy
  • Tumor Cells, Cultured


  • Cytokines