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Cbx3/HP1? deficiency confers enhanced tumor-killing capacity on CD8+ T cells.

ABSTRACT: Cbx3/HP1? 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?-insufficient mice or wild type mice treated with Cbx3/HP1?-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?-insufficient mice or wild type mice treated with Cbx3/HP1?-insufficient CD8+ T cells. These findings suggest that targeting Cbx3/HP1? can represent a rational therapeutic approach to control growth of solid tumors.

SUBMITTER: Sun M

PROVIDER: S-EPMC5318867 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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

Sun Michael M Ha Ngoc N Pham Duc-Hung DH Frederick Megan M Sharma Bandana B Naruse Chie C Asano Masahide M Pipkin Matthew E ME George Rani E RE Thai To-Ha TH

Scientific reports 20170221

Cbx3/HP1γ is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8+ T cells, Cbx3/HP1γ insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8+ T cells, there is an increase of CD8+ effector T cells expressing the stimulatory receptor Klrk1/NKG2D, a d ...[more]

PMID: 28220815

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