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Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells

View Article: PubMed Central - PubMed

ABSTRACT

Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- γ against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.

No MeSH data available.


Related in: MedlinePlus

Effects of treatment with decitabine, ionizing radiation (IR), or their combination on IFN-γ production in NK cells against target tumor cells.Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h. Then the cell supernatants were harvested and analyzed by ELISA. Results express the average IFN-γ production ± SD in NK cells co-cultured with A549, HCT-116, and HepG2 cells. Experiments were independently performed from five healthy donors. The assay was performed in triplicated each donor. Statistical significance was determined using a one-way ANOVA.
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f7: Effects of treatment with decitabine, ionizing radiation (IR), or their combination on IFN-γ production in NK cells against target tumor cells.Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h. Then the cell supernatants were harvested and analyzed by ELISA. Results express the average IFN-γ production ± SD in NK cells co-cultured with A549, HCT-116, and HepG2 cells. Experiments were independently performed from five healthy donors. The assay was performed in triplicated each donor. Statistical significance was determined using a one-way ANOVA.

Mentions: Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h, and IFN-γ levels were subsequently determined in the culture supernatants. As shown in Fig. 7, NK cells alone spontaneously produced very low levels of IFN-γ. Treatment with decitabine or IR did not affect the production of IFN-γ in NK cells compared with untreated target tumor cells. Furthermore, the combination treatment of decitabine and IR also showed a pattern similar to single treatment in IFN-γ production of NK cells. These results suggest that decitabine, IR, or their combination treatment of target tumor cells could not improve the susceptibility of tumor cells to NK cells.


Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells
Effects of treatment with decitabine, ionizing radiation (IR), or their combination on IFN-γ production in NK cells against target tumor cells.Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h. Then the cell supernatants were harvested and analyzed by ELISA. Results express the average IFN-γ production ± SD in NK cells co-cultured with A549, HCT-116, and HepG2 cells. Experiments were independently performed from five healthy donors. The assay was performed in triplicated each donor. Statistical significance was determined using a one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037374&req=5

f7: Effects of treatment with decitabine, ionizing radiation (IR), or their combination on IFN-γ production in NK cells against target tumor cells.Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h. Then the cell supernatants were harvested and analyzed by ELISA. Results express the average IFN-γ production ± SD in NK cells co-cultured with A549, HCT-116, and HepG2 cells. Experiments were independently performed from five healthy donors. The assay was performed in triplicated each donor. Statistical significance was determined using a one-way ANOVA.
Mentions: Tumor cells treated with decitabine and/or IR were co-cultured with NK cells for 4 h, and IFN-γ levels were subsequently determined in the culture supernatants. As shown in Fig. 7, NK cells alone spontaneously produced very low levels of IFN-γ. Treatment with decitabine or IR did not affect the production of IFN-γ in NK cells compared with untreated target tumor cells. Furthermore, the combination treatment of decitabine and IR also showed a pattern similar to single treatment in IFN-γ production of NK cells. These results suggest that decitabine, IR, or their combination treatment of target tumor cells could not improve the susceptibility of tumor cells to NK cells.

View Article: PubMed Central - PubMed

ABSTRACT

Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- γ against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.

No MeSH data available.


Related in: MedlinePlus