Abstract
Breast cancer (BC) is the number one cause of deaths from cancer in women. Metastasis in BC is caused by immunosurveillance deficiency, including impairment of Natural Killer (NK) cell maturation, low NK activity, and decreasing cytotoxicity. This study was performed to improve activating receptors and cytotoxicity of NK cells using interleukin 15 (IL15) against BC cells. Human recombinant IL15 was used to induce NK cells. To evaluate the potential of IL15 in inducing NK cells, we measured the activating and inhibiting receptors (NKG2D, NKG2A), apoptotic potency of NK cells on BC cells (MCF7) using transwell assay. The IL15 inducer on the NK cell were measured NKG2D, NKG2A gene expression with quantitative polymerase chain reaction (qPCR), (GzmB) secretion using ELISA, apoptotic gene expression of MCF7 using qPCR. IL15 increased NKG2D expression 4.01-9.13%, but IL15 could not affect toward NKG2A expression on NK cells. IL15-activated NK cells, inhibited BC cells proliferation, induced apoptotic BC cells 25.89-32.19%, induced apoptotic genes of BC cells bax, p53. IL15 increase NK activating receptor (NKG2D), inhibit BC cells proliferation, induce apoptotic percentage and induce apoptotic gene expression.
Highlights
Breast cancer (BC) is one of the main causes of death in the world
Effect of interleukin 15 (IL15) toward Natural Killer (NK) Cell Characteristics To determine the effect of human recombinant IL15 toward NK receptors, we evaluated the NK receptors including gene expression of NKG2D and NKG2A (Figure 1)
The data showed that IL15 (5, 10 ng/ml) significantly up-regulated NKG2D, IL15 did not significantly down-regulate NKG2A
Summary
Breast cancer (BC) is one of the main causes of death in the world. In 2012, it caused around 8.2 million deaths (Ferlay et al 2015). Immunotherapy using NK cells can be used to obtain the large and sufficient numbers of functional NK cells necessary for clinical therapy. The number, purity and state of NK cell proliferation and activation are key factors in immunotherapy (Cheng et al 2013). NK cells are known as necessary effectors in suppressing cancer proliferation (Kelly et al 2003; Smyth et al 2005). Once NK cells recognize target cells such as cancer cells, they form an immunological synapse, and the secretory granules fuse with the presynaptic membrane and release perforin (Prf) and granzyme (Gzm) into the synaptic cleft. Released Prf provides transmembrane pores on the target cell
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