Work

The histone demethylase Utx controls CD8 + T‐cell‐dependent antitumor immunity via epigenetic regulation of the effector function

Year: 2023

Type: article

Abstract: CD8+ T cells play a central role in antitumor immune responses. Epigenetic gene regulation is essential to acquire the effector function of CD8+ T cells. However, the role of Utx, a demethylase of histone H3K27, in antitumor immunity remains unclear. In this study, we examined the roles of Utx in effector CD8+ T‐cell differentiation and the antitumor immune response. In a murine tumor‐bearing model, an increased tumor size and decreased survival rate were observed in T‐cell‐specific Utx KO (Utx KO) mice compared with wild‐type (WT) mice. The number of CD8+ T cells in tumor‐infiltrating lymphocytes (TILs) was significantly decreased in Utx KO mice. We found that the acquisition of effector function was delayed and attenuated in Utx KO CD8+ T cells. RNA sequencing revealed that the expression of effector signature genes was decreased in Utx KO effector CD8+ T cells, while the expression of naïve or memory signature genes was increased. Furthermore, the expression of Cxcr3, which is required for the migration of effector CD8+ T cells to tumor sites, was substantially decreased in Utx KO CD8+ T cells. These findings suggest that Utx promotes CD8+ T‐cell‐dependent antitumor immune responses partially through epigenetic regulation of the effector function.

Source: Cancer Science

DOI: 10.1111/cas.15814