Decitabine treatment sensitizes tumor cells to T-cell-mediated cytotoxicity in patients with myelodysplastic syndromes.
Decitabine treatment improves immunological recognition that increases expression of cancer-testis antigens (CTAs) against solid tumors. The mechanisms of decitabine enhancement of immunogenicity when used for patients with myelodysplastic syndromes (MDS) remain unclear. In the present study, we found relatively low baseline expression of MAGE-A1, MAGE-A3, and SP17 in MDS-derived cell lines. Decitabine treatment significantly improved MAGE-A1, MAGE-A3, and SP17 expression in these cell lines and in MDS patients. Decitabine-treated K562 and SKM-1 target cells with incrementally induced MAGE-A1, MAGE-A3, or SP17 levels up-regulated T lymphocyte function. Decitabine treatment improved CTA-specific cytotoxic T lymphocyte (CTL) recognition of MDS cells via the up-regulation of CTAs. This response was accompanied by enhanced T lymphocyte function and HLA class antigen expression, and increased ICAM-1. These findings suggested that decitabine may have a broad range of therapeutic applications when it is used in association with active adaptive immunity responses against up-regulated CTAs.
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Zheng
Z
Zhang
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Qi
Q
He
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Ying
Y
Tao
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Juan
J
Guo
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Feng
F
Xu
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Ling-Yun
LY
Wu
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
You-Shan
YS
Zhao
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Dong
D
Wu
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Li-Yu
LY
Zhou
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Ji-Ying
JY
Su
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Lu-Xi
LX
Song
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Chao
C
Xiao
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Xiao
X
Li
Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Chun-Kang
CK
Chang
Myelodysplastic syndromes; T cytotoxicity; cancer-testis antigens; decitabine