Reactome | Regulation of PD-L1(CD274) transcription

Regulation of PD-L1(CD274) transcription

Stable Identifier

R-HSA-9909649

DOI

10.3180/R-HSA-9909649.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Regulation of PD-L1(CD274) transcription

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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)

Literature References

PubMed ID	Title	Journal	Year
32064150	Regulation of PD-L1 expression in cancer and clinical implications in immunotherapy Ju, X, Zhang, H, Zhou, Z, Wang, Q	Am J Cancer Res	2020
31668929	Mechanisms Controlling PD-L1 Expression in Cancer Cha, JH, Chan, LC, Li, CW, Hsu, JL, Hung, MC	Mol Cell	2019
35132224	Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics Yamaguchi, H, Hsu, JM, Yang, WH, Hung, MC	Nat Rev Clin Oncol	2022
32504749	PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs Ashrafizadeh, M, Zarrabi, A, Hushmandi, K, Zarrin, V, Moghadam, ER, Zabolian, A, Tavakol, S, Samarghandian, S, Najafi, M	Life Sci	2020
37228770	PD-L1: expression regulation Zhou, YJ, Li, G, Wang, J, Liu, M, Wang, Z, Song, Y, Zhang, X, Wang, X	Blood Sci	2023