biostudies-literatureUnknown9(21)Huang CImmune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) have enabled some patients with cancer to experience durable, complete treatment responses; however, reliable anti-PD-(L)1 treatment response biomarkers are lacking. Our research found that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Furthermore, PD-L1 K162 methylation controlled the PD-1/PD-L1 interaction and obviously enhanced the suppression of T cell activity controlling cancer immune surveillance. We demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, investigated that PD-L1 K162 methylation was a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed Science advanceseade4186https://www.ebi.ac.uk/biostudies/studies/S-EPMC10219601biostudies-literaturePD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance.PMC10219601Chu QHuang CZheng XWu QSong DWang GJiang TZou CWang JJia KSun LHu FLi YHu JLiu AChen YLuo XRen SLv PLan JfalsePD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance.Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) have enabled some patients with cancer to experience durable, complete treatment responses; however, reliable anti-PD-(L)1 treatment response biomarkers are lacking. Our research found that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Furthermore, PD-L1 K162 methylation controlled the PD-1/PD-L1 interaction and obviously enhanced the suppression of T cell activity controlling cancer immune surveillance. We demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, investigated that PD-L1 K162 methylation was a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed 2023-01-01T00:00:00Z2023 May2025-04-19T23:00:51.918Z2025-04-19T23:00:51.918ZS-EPMC102196013723565610.1126/sciadv.ade4186