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

• Published in: Scientific reports Vol. 6; no. 1; p. 32470
• Main Authors: Son, Cheol-Hun, Lee, Hong-Rae, Koh, Eun-Kyoung, Shin, Dong-Yeok, Bae, Jae-Ho, Yang, Kwangmo, Park, You-Soo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.09.2016; Nature Publishing Group
• Subjects: 13; 13/2; 13/31; 5-aza-2'-deoxycytidine; 631/250/251/1567; 692/4028/67/1059/2325; Antitumor agents; Cancer; Cytotoxicity; Humanities and Social Sciences; I.R. radiation; Immunogenicity; Interferon; Ionizing radiation; Lymphocytes T; Major histocompatibility complex; multidisciplinary; Natural killer cells; NKG2 antigen; Science; Science (multidisciplinary); Tumor cells; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep32470

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.