Entry
Name
PD-L1 expression and PD-1 checkpoint pathway in cancer - Equus przewalskii (Przewalski's horse)
Description
Programmed cell death 1 (PD1) and its ligand (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. In solid tumors, the PD-1/PD-L1 inhibitory pathway can be (mis-)used to silence the immune system by increasing the expression of PD-L1 on the tumor cell surface. Up-regulation of PD-L1 is caused by activation of pro-survival pathways MAPK and PI3K/Akt as well as transcriptional factors HIF-1, STAT3 and NF-kappa B. The MAPK and PI3K signalling pathways are activated by gene mutations and growth factors. PD-L1 on tumor cells may then engage the PD-1 receptors resulting in suppression of T-cell mediated immune response. Therapeutic antibodies blocking the PD-1/PD-L1 pathway by targeting PD-L1 or PD-1 are highly effective in rescuing T cell anti-tumor effector functions.
Class
Human Diseases; Cancer: overview
BRITE hierarchy
Pathway map
epz05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Ortholog table
Organism
Equus przewalskii (Przewalski's horse) [GN:
epz ]
Gene
103548618 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
103557606 EML4; echinoderm microtubule associated protein like 4 [KO:K15420 ]
103548220 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
103551868 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
103561550 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
103548655 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
103550364 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
103563745 nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446 ]
103554320 BATF3; basic leucine zipper ATF-like transcription factor 3 [KO:K09034 ]
103548624 BATF; basic leucine zipper ATF-like transcription factor [KO:K09034 ]
103559136 BATF2; basic leucine zipper ATF-like transcription factor 2 [KO:K09034 ]
103548960 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
103552460 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Kythreotou A, Siddique A, Mauri FA, Bower M, Pinato DJ
Title
PD-L1.
Journal
Reference
Authors
Zhou TC, Sankin AI, Porcelli SA, Perlin DS, Schoenberg MP, Zang X
Title
A review of the PD-1/PD-L1 checkpoint in bladder cancer: From mediator of immune escape to target for treatment.
Journal
Reference
Authors
Wang Y, Wang H, Yao H, Li C, Fang JY, Xu J
Title
Regulation of PD-L1: Emerging Routes for Targeting Tumor Immune Evasion.
Journal
Reference
Authors
Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, Wu X, Ma J, Zhou M, Li X, Li Y, Li G, Xiong W, Guo C, Zeng Z
Title
Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.
Journal
Reference
Authors
Bardhan K, Anagnostou T, Boussiotis VA
Title
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.
Journal
Reference
Authors
Shi Y
Title
Regulatory mechanisms of PD-L1 expression in cancer cells.
Journal
Reference
Authors
Zerdes I, Matikas A, Bergh J, Rassidakis GZ, Foukakis T
Title
Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
Journal
Reference
Authors
Chen J, Jiang CC, Jin L, Zhang XD
Title
Regulation of PD-L1: a novel role of pro-survival signalling in cancer.
Journal
Reference
Authors
Glodde N, Holzel M
Title
RAS and PD-L1: A Masters' Liaison in Cancer Immune Evasion.
Journal
Reference
Authors
Ritprajak P, Azuma M
Title
Intrinsic and extrinsic control of expression of the immunoregulatory molecule PD-L1 in epithelial cells and squamous cell carcinoma.
Journal
Reference
Authors
Nirschl CJ, Drake CG
Title
Molecular pathways: coexpression of immune checkpoint molecules: signaling pathways and implications for cancer immunotherapy.
Journal
Reference
Authors
Saeidi A, Zandi K, Cheok YY, Saeidi H, Wong WF, Lee CYQ, Cheong HC, Yong YK, Larsson M, Shankar EM
Title
T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses.
Journal
Reference
Authors
Sharpe AH, Pauken KE
Title
The diverse functions of the PD1 inhibitory pathway.
Journal
Reference
Authors
Boussiotis VA
Title
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway.
Journal
Reference
Authors
Arasanz H, Gato-Canas M, Zuazo M, Ibanez-Vea M, Breckpot K, Kochan G, Escors D
Title
PD1 signal transduction pathways in T cells.
Journal
Reference
Authors
Zuazo M, Gato-Canas M, Llorente N, Ibanez-Vea M, Arasanz H, Kochan G, Escors D
Title
Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy.
Journal
Reference
Authors
Patsoukis N, Li L, Sari D, Petkova V, Boussiotis VA
Title
PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2.
Journal
Reference
Authors
Chinai JM, Janakiram M, Chen F, Chen W, Kaplan M, Zang X
Title
New immunotherapies targeting the PD-1 pathway.
Journal
Reference
Authors
Ok CY, Young KH
Title
Targeting the programmed death-1 pathway in lymphoid neoplasms.
Journal
Related pathway
epz04620 Toll-like receptor signaling pathway
epz04660 T cell receptor signaling pathway
KO pathway
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