Abstract
Natural Killer (NK) cell has the capability to immunosensitize and cell-mediated lysis of many types of cancer cells, however, most of the cancer cells are evading the NK cell-mediated lysis by down-regulating the NK cell specific ligands. In the present study, we have evaluated the comparative and synergic effect of spironolactone (SPIR) and AVE in enhancing the susceptibility of osteosarcoma cells (MG-63) to NK cell-mediated lysis in vitro. The NK cells used in this study was characterised by the expression of CD56 and NKG2D using flow cytometry. At an optimized concentration, SPIR (60 μM) and AVE (5 mg/ml) treatment showed significant upregulation of the NK cell-specific NKG2D ligands (MICA, MICB, ULP1, and ULP2) expression in MG-63 cells compared to those in untreated group. To evaluate the NK cell sensitisation towards osteosarcoma cells, MG-63 cells were treated with and without SPIR and AVE for 72 hrs, followed by co-culturing with NK cells [different target and effector ratio (E:T), 1:1, 1:2, 1:5, 1:10 and 1:20] for different time periods (4 and 24 hrs). Cytotoxicity analysis reveals that AVE and AVE+SPIR combination treated MG-63 cells are more susceptible to NK cell-mediated lysis than those SPIR treated in time and dose (E: T ratio) dependent manner. In conclusion, SPIR and AVE are potentially enhancing the NK cell mediate lysis of osteosarcoma cells by unregulated the NK cell specific ligands.
Highlights
Treating osteosarcoma (OS) remains as a challenge attributed to the overall survival rate of 5 years to be 67% and not been improved for the past two decades with existing treatments [1]
Our results demonstrated that the synergetic effect of SPIR and AVE enhanced the susceptibility of OS cells to Natural Killer (NK) cell-mediated lysis by up-regulating the NKG2D ligands
The analysis revealed that purity and anti-tumor functionality of ex-vivo expanded NK cells were more than 95% (Figure 1)
Summary
Treating osteosarcoma (OS) remains as a challenge attributed to the overall survival rate of 5 years to be 67% and not been improved for the past two decades with existing treatments [1]. Conventional cancer therapies confer survival benefits for OS patients, but they often associated with many side effects and tumor relapse which leads a compromised quality of life. There is a desperate need to establish new improved therapeutic strategies to have better treatment outcomes in OS patients. Adoptive immunotherapy is rapidly growing as an alternative to conventional treatment for OS. The effect of anti-tumor immune response is varied as based on the type of adoptive immune cells used. Nature Killer (NK) cells have gained immense attention in immunotherapy for many cancer types, including OS [1,2,3]
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