Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells.
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.
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.
Cheol-Hun
CH
Son
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.|Department of Biochemistry, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea.
Hong-Rae
HR
Lee
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.
Eun-Kyoung
EK
Koh
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.
Dong-Yeok
DY
Shin
Department of Biochemistry, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea.
Jae-Ho
JH
Bae
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.
Kwangmo
K
Yang
Department of Research Center, Dongnam Institute of Radiological &Medical Sciences, Jwadong-gil 40, Jangan-eup, Gijang-gun, Busan, 46033, Republic of Korea.
You-Soo
YS
Park
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