| First Author | Noda H | Year | 2023 |
| Journal | Cancer Sci | Volume | 114 |
| Issue | 7 | Pages | 2787-2797 |
| PubMed ID | 37068788 | Mgi Jnum | J:347057 |
| Mgi Id | MGI:7520708 | Doi | 10.1111/cas.15814 |
| Citation | Noda H, et al. (2023) The histone demethylase Utx controls CD8(+) T-cell-dependent antitumor immunity via epigenetic regulation of the effector function. Cancer Sci 114(7):2787-2797 |
| abstractText | 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 naive 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. |
