Although ICB therapies targeting PD-1–programmed cell death ligand 1 (PD-L1) interaction have documented durable remissions in a subset of patients with cancer, the overall response rates remain modest and even inert in certain cancer types3, which might be partially explained by the fact that ICB therapies do not fundamentally alter the exhaustion-inherited epigenetic program in TEX cells and fail to reprogram these cells to differentiate into TMEM cells4,5. This evidence concerns the gene CD274 and cancer.