Demethylating agent decitabine induces autologous cancer testis antigen specific cytotoxic T lymphocytes in vivo  

作　　者：ZHOU Ji-hao YAO Yu-shi WANG Li-xin WANG Jia LI Yong-hui JIANG Meng-meng ZHOU Min-hang GAO Xiao-ning LI Rui-sheng WANG Li-li YU Li 

机构地区：[1]Department of Hematology, Chinese People's Liberation Army General Hospital, Beijing 100853, China [2]Animal Laboratory Center, 302 Hospital of People's LiberationArmy, Beijing 100039, China

出　　处：《Chinese Medical Journal》2013年第23期4552-4556,共5页中华医学杂志（英文版）

基　　金：This work was supported by the grants from the National Basic Research Program of China （No. 2005CB522400）, National Natural Science Foundation of China （Nos. 90919044, 30971297, 81000221 and 81170518）, Capital Medical Development Scientific Research Fund （No. 2007-2040）, National Public Health Grand Research Foundation （No. 201202017） and The Capital of the Public Health Project （No. Z 111107067311070）. Conflict of interest： none.

摘　　要：Background Cancer testis antigens （CTAs） are a novel group of tumor associated antigens.Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism,thus enhance the immunogenicity of leukemia cells.However,few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes （CTLs） in vivo,and if so,whether this effect contributes to disease control.In this study,we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo.Methods Several mouse CTAs were screened by RT-PCR.CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry.The activity of specific CTLs was measured by real time RT-PCR.Results We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs.Then we measured the CTLs＇ activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment.Finally,we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells.Conclusions Our study showed the autologous immune response induced by decitabine in vivo.And more importantly,we firstly proved that this response may contribute to disease control.We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine,and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.Background Cancer testis antigens （CTAs） are a novel group of tumor associated antigens.Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism,thus enhance the immunogenicity of leukemia cells.However,few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes （CTLs） in vivo,and if so,whether this effect contributes to disease control.In this study,we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo.Methods Several mouse CTAs were screened by RT-PCR.CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry.The activity of specific CTLs was measured by real time RT-PCR.Results We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs.Then we measured the CTLs＇ activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment.Finally,we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells.Conclusions Our study showed the autologous immune response induced by decitabine in vivo.And more importantly,we firstly proved that this response may contribute to disease control.We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine,and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.

关 键 词：DECITABINE cancer testis antigens AUTOLOGOUS cytotoxic T lymphocytes 

分 类 号：R737.21[医药卫生—肿瘤]