CD34+ progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rgnull mice

Autor: Jolien M.R. Van der Meer, Paul K.J.D. de Jonge, Anniek B. van der Waart, Alexander C. Geerlings, Jurgen P. Moonen, Jolanda Brummelman, Janne de Klein, Malou C. Vermeulen, Ralph J.A. Maas, Nicolaas P.M. Schaap, Janneke S. Hoogstad-van Evert, Petronella B. Ottevanger, Joop H. Jansen, Willemijn Hobo, Harry Dolstra
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: OncoImmunology, Vol 10, Iss 1 (2021)
Druh dokumentu: article
ISSN: 2162-402X
2162402X
DOI: 10.1080/2162402X.2021.1981049
Popis: Combining natural killer (NK) cell adoptive transfer with tumor-sensitizing chemotherapy is an attractive approach against recurrent ovarian cancer (OC), as OC is sensitive to NK cell-mediated immunity. Previously, we showed that CD34+ hematopoietic progenitor cell (HPC)-derived NK cells can kill OC cells in vitro and inhibit OC tumor growth in mice. Here, we investigated the potential of HPC-NK cell therapy combined with chemotherapeutic gemcitabine (used in recurrent OC patients) against OC. We examined the phenotypical, functional, and cytotoxic effects of gemcitabine on HPC-NK cells and/or OC cells in vitro and in OC-bearing mice. To this end, we treated OC cells and/or HPC-NK cells with or without gemcitabine and analyzed the phenotype, cytokine production, and anti-tumor reactivity. We found that gemcitabine did not affect the phenotype and functionality of HPC-NK cells, while on OC cells expression of NK cell activating ligands and death receptors was upregulated. Although gemcitabine pre-treatment of OC cells did not improve the functionality of HPC-NK cells, importantly, HPC-NK cells and gemcitabine additively killed OC cells in vitro. Similarly, combined HPC-NK cell and gemcitabine treatment additively decreased tumor growth in OC-bearing mice. Collectively, our results indicate that combination therapy of HPC-NK cells and gemcitabine results in augmented OC killing in vitro and in vivo. This provides a rationale for exploring this therapeutic strategy in patients with recurrent OC.
Databáze: Directory of Open Access Journals
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