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

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 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/HP1γ-insufficient mice or wild type mice treated with Cbx3/HP1γ-insufficient CD8 T cells. These findings suggest that targeting Cbx3/HP1γ can represent a rational therapeutic approach to control growth of solid tumors.