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

Abstract

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.

• Authors: Ji-hao Zhou, Yu-shi Yao, Li-xin Wang, Jia Wang, Yong-hui Li, Meng-meng Jiang, Min-hang Zhou, Xiao-ning Gao, Rui-sheng Li, Li-li Wang, Li Yu
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 126 Issue 23 Pg. 4552-6 (Dec 2013) ISSN: 2542-5641 [Electronic] China
• PMID: 24286424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antimetabolites, Antineoplastic
• Decitabine
• Azacitidine

Topics

• Animals
• Antigens, Neoplasm (metabolism)
• Antimetabolites, Antineoplastic (pharmacology)
• Azacitidine (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Decitabine
• Flow Cytometry
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• T-Lymphocytes, Cytotoxic (drug effects, metabolism)