Regulation of PD-L1(CD274) transcription

The transcriptional regulation of CD274 (PD-L1/ programmed death-ligand 1) plays a critical role in the regulation of normal T cell function in normal physiological condition where it provides immune homeostasis. The expression of PD-L1 is tightly controlled by various transcription factors and signalling pathways, which respond to both intrinsic cellular signals and extrinsic environmental perturbations. PD-L1 is regulated transcriptionally by multiple mechanism like epigenetic modifications (EZH2, DNMTs, MLLs), transcription factors (STAT3. STAT1, IRF1, MYC, HIF and ither) which get activated in response to multiple upstream signalling pathways. The transcriptional regulation of PD-L1 is a complex interplay of oncogenic signalling pathways, cytokine responses, epigenetic modifications, specific transcription factors, the tumour microenvironment, and non-coding RNAs. This multifaceted regulation ensures that PD-L1 expression can be finely tuned to promote immunotolerance in normal condition as well as immune evasion in cancer, making it a critical target for cancer immunotherapy (Zhou et al.,2023, Cha et al.,2019, Yamaguchi et al.,2022, Ju et al.,2020)

Summary from Reactome (R-HSA-9909649), read 2026-09-23.