Affiliation:
1. Ankara University: Ankara Universitesi
2. Ankara Üniversitesi: Ankara Universitesi
Abstract
Abstract
Natural killer (NK) cells are immune cells that have attracted significant attention due to their cytotoxic properties. They are believed to be highly effective in cancer therapy. In this study, anti-KIR2DL4 (Killer cell Immunoglobulin like Receptor, 2 Ig Domains and Long cytoplasmic tail 4) was used to stimulate the NK-92 activator receptor to increase their cytotoxicity on breast cancer cell lines. Unstimulated and stimulated NK-92 cells (sNK-92) were cocultured with breast cancer (MCF-7 and SK-BR-3) and normal breast (MCF-12A) cell lines at 1:1, 1:5, and 1:10 (Target: Effector) ratios. The most effective cell cytotoxicity ratio (1:10) was used in the immunostaining and western blot assays to evaluate apoptosis pathway proteins. The sNK-92 cells showed higher cytotoxic activity on breast cancer cells than NK-92 cells. sNK-92 cells had a selective significant cytotoxicity effect on MCF-7 and SK-BR-3 cells but not MCF-12A cells. While sNK-92 cells were effective at all cell concentrations, they were most effective at a 1:10 ratio. Immunostaining and western blots showed significantly higher BAX, caspase 3, and caspase 9 protein levels in all breast cancer cell groups cocultured with sNK-92 than with NK-92 cells. NK-92 cells stimulated with KIR2DL4 showed elevated cytotoxic activity. The cytotoxic activity of sNK-92 cells on breast cancer cells is via apoptosis pathways. However, their effect on normal breast cells is limited. While the obtained data contains only basic information, additional clinical studies are needed to provide a basis for a new treatment model.
Publisher
Research Square Platform LLC
Reference35 articles.
1. Hanahan D, Weinberg RA. The hallmarks of cancer. cell 2000;100(1):57–70
2. Zhou J. Advances and prospects in cancer immunotherapy. New Journal of Science 2014;2014
3. MicroRNA 603 acts as a tumor suppressor and inhibits triple negative breast cancer tumorigenesis by targeting elongation factor 2 kinase;Bayraktar R;Oncotarget,2017
4. Natural killer cell activities of patients with breast cancer against different target cells;Hamilton G;J Cancer Res Clin Oncol,1988
5. PD-L1 expression in triple-negative breast cancer;Mittendorf EA;Cancer Immunol Res,2014