Targeting Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunity - PubMed
3 hours ago
- #Cancer Immunotherapy
- #Epigenetic Regulation
- #CD8+ T Cells
- CD8+ T cell exhaustion limits cancer immunotherapy effectiveness.
- Mettl8 is an RNA methyltransferase highly expressed in stem-like progenitor exhausted T (TPEX) cells.
- Mettl8 stabilizes Tcf7 mRNA via m3C modification and enhances Tcf1 protein expression.
- Mettl8 deletion or inhibition promotes TPEX differentiation into intermediate exhausted T cells, improving antitumor immunity.
- Combining Mettl8 inhibition with anti-PD-1 therapy shows synergistic efficacy in tumor control.
- Mettl8 interacts with Tcf1 to regulate chromatin looping at the Tox locus, maintaining TPEX stemness.