Downregulation of Ezh2 promotes the differentiation of short-lived effector CD8 T cells and weakens antitumor immunity

We found that although the expression of effector molecules was rapidly increased in Ezh2 KO CD8⁺ T cells compared to WT cells, apoptotic cell death was also rapidly induced after activation. RNA-sequencing revealed that the expression of effector signature genes was upregulated in Ezh2 KO effector CD8⁺ T cells, along with the expression of apoptosis-related genes. These findings suggest that Downregulation of Ezh2 promotes the differentiation of short-lived effector CD8 T cells and weakens antitumor immunity.

These findings suggest that downregulation of Ezh2 promotes the differentiation of short-lived effector CD8⁺ T cells and impairs sustained antitumor immunity. Maintaining appropriate levels of H3K27 trimethylation may be essential for the long-term persistence of effective antitumor T cell responses.