Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8+ T cells

被引：16

作者：

Sun, Michael ^{[1
]}

Ha, Ngoc ^{[1
,2
]}

Pham, Duc-Hung ^{[1
,3
]}

Frederick, Megan ^{[4
]}

Sharma, Bandana ^{[5
,6
]}

Naruse, Chie ^{[7
]}

Asano, Masahide ^{[7
]}

Pipkin, Matthew E. ^{[4
]}

George, Rani E. ^{[5
,6
,8
]}

Thai, To-Ha ^{[1
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA

[2] Drexel Univ, Dept Neurobiol & Anat, Coll Med, 2900 Queen Lane, Philadelphia, PA 19129 USA

[3] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA

[4] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA

[5] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02215 USA

[6] Boston Childrens Hosp, Boston, MA 02215 USA

[7] Kyoto Univ, Inst Lab Anim, Grad Sch Med, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan

[8] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

ANTI-GD2; MONOCLONAL-ANTIBODY; HETEROCHROMATIN PROTEIN-1; TRANSCRIPTION ELONGATION; NKG2D; HP1-GAMMA; METHYLATION; THERAPY; HP1; MECHANISMS; EXHAUSTION;

D O I：

10.1038/srep42888

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cbx3/HP1 gamma is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8(+) T cells, Cbx3/HP1. insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1 gamma-insufficient mice or wild type mice treated with Cbx3/HP1 gamma-insufficient CD8(+) T cells, there is an increase of CD8(+) effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a decrease in CD4(+) CD25(+) FOXP3(+) regulatory T cells (Treg cells) as well as CD25(+) CD4(+) T cells expressing the inhibitory receptor CTLA4. Together these changes in the tumor immune environment may have mitigated tumor burden in Cbx3/HP1 gamma-insufficient mice or wild type mice treated with Cbx3/HP1 gamma-insufficient CD8(+) T cells. These findings suggest that targeting Cbx3/HP1. can represent a rational therapeutic approach to control growth of solid tumors.

引用

页数：12

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