Cbx3/HP1Î 3 deficiency confers enhanced tumor-killing capacity on CD8 + T cells

Abstract

Cbx3/HP1Î 3 is a histone reader whose function in the immune system is not completely understood. Here, we demonstrate that in CD8 + T cells, Cbx3/HP1Î 3 insufficiency leads to chromatin remodeling accompanied by enhanced Prf1, Gzmb and Ifng expression. In tumors obtained from Cbx3/HP1Î 3-insufficient mice or wild type mice treated with Cbx3/HP1Î 3-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/HP1Î 3-insufficient mice or wild type mice treated with Cbx3/HP1Î 3-insufficient CD8 + T cells. These findings suggest that targeting Cbx3/HP1Î 3 can represent a rational therapeutic approach to control growth of solid tumors.