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

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

Author information

1
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Rm 4015 Michael DeGroote Centre for Learning and Discovery, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
2
Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
3
The Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA.
4
Division of Medical Oncology, Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada.
5
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Rm 4015 Michael DeGroote Centre for Learning and Discovery, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada. ashkara@mcmaster.ca.

Abstract

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

PMID:
29299659
DOI:
10.1007/s00262-017-2112-x
[Indexed for MEDLINE]

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