Reactome | Regulation of PD-L1(CD274) expression

Regulation of PD-L1(CD274) expression

Stable Identifier

R-HSA-9909648

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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The PD-L1(CD274)/PD1 pathways play a pivotal role in the regulation of normal T cell function as well in diseases like Cancer. It is a major co-inhibitory checkpoint signalling that regulates T cell activities and maintains immune homeostasis thus preventing autoimmunity in normal physiology (Cha et al., 2019) and this same machinery is hijacked in disease like cancer to evade T-cells immunity against cancer cells (Ju et al., 2020, Zhou et al., 2023). Under normal physiological conditions, PDL-1 (CD274) binds with its receptor PD1 and inhibits TCR and costimulatory signalling, thus inhibiting T cell activation (Arasanz et al. 2017, Riley et al.,2009, Sharpe et al., 2018). This regulation helps in the maintenance of immune tolerance. PDL1 (CD274) is normally expressed by antigen presenting cells APCs but it's also found to be expressed by non-immune cells like cancer cells (Cha et al., 2019, Chen et al., 2016. Expression of PDL1 is highly up regulated in cancers to evade the immune response by T cells thus making it a critical target for cancer treatment which leads to rapid FDA approval of drugs targeting PDL1/PD1 pathway (Ju et al., 2020, Yamaguchi et al. 2023, Wu et al.,2021). Expression of PDL1 is tightly controlled at epigenetics, transcriptional, translational and post translational level in normal condition but cancer cells utilise this regulation to induce PDL1 expression on its surface. (Cha et al., 2019, Ju et al, 2020, Zhou et al, 2023).

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
28990585	The diverse functions of the PD1 inhibitory pathway Sharpe, AH, Pauken, KE	Nat Rev Immunol	2018
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
26681673	Regulation of PD-L1: a novel role of pro-survival signalling in cancer Chen, J, Jiang, CC, Jin, L, Zhang, XD	Ann Oncol	2016
19426218	PD-1 signaling in primary T cells Riley, JL	Immunol Rev	2009
37228770	PD-L1: expression regulation Zhou, YJ, Li, G, Wang, J, Liu, M, Wang, Z, Song, Y, Zhang, X, Wang, X	Blood Sci	2023
28881701	PD1 signal transduction pathways in T cells Arasanz, H, Gato-Cañas, M, Zuazo, M, Ibañez-Vea, M, Breckpot, K, Kochan, G, Escors, D	Oncotarget	2017