Targeting Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunity
Jiaxi Song·Fengyin Li·Lilin Ye·J. Ma·Jiabao Wang·Jing Yang·Qizhao Huang·Dan Cui·Qing Liu·Xuewei Qi·Jia Li·Haoyu Yu
CD8+ T cell exhaustion represents a major obstacle to effective cancer immunotherapy. While stem-like progenitor exhausted T (TPEX) cells can differentiate into intermediate (Int-TEX) and terminally exhausted (TEX) subsets, the epigenetic regulation of this process is unclear. We identify the RNA methyltransferase Mettl8 as a critical regulator, with expression significantly higher in TPEX than in TEX subsets. In anti-PD-1 responding non-small cell lung cancer patients, Mettl8 and the stemness f