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CD34 + progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg null mice.
- Source :
-
Oncoimmunology [Oncoimmunology] 2021 Oct 01; Vol. 10 (1), pp. 1981049. Date of Electronic Publication: 2021 Oct 01 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- 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 <superscript>+</superscript> 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.<br />Competing Interests: None of the authors have any competing interests.<br /> (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Details
- Language :
- English
- ISSN :
- 2162-402X
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncoimmunology
- Publication Type :
- Academic Journal
- Accession number :
- 34616589
- Full Text :
- https://doi.org/10.1080/2162402X.2021.1981049