Entry Name PD-L1 expression and PD-1 checkpoint pathway in cancer - Dasypus novemcinctus (nine-banded armadillo)
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: overviewBRITE hierarchy
Pathway map dnm05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Ortholog table Organism Dasypus novemcinctus (nine-banded armadillo) [GN:
dnm ]
Gene 101418354 EML4; echinoderm microtubule-associated protein-like 4 [KO:K15420 ]
101423744 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
101435351 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101433347 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101444276 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101443761 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101426945 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101412730 NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734 ]
101437556 NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
101436399 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
101444225 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
101445854 TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403 ]
101431630 MYD88; LOW QUALITY PROTEIN: myeloid differentiation primary response protein MyD88 [KO:K04729 ]
101427882 NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
101417008 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
101424450 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X2 [KO:K17333 ]
101437864 BATF2; basic leucine zipper transcriptional factor ATF-like 2 [KO:K09034 ]
101421192 BATF3; basic leucine zipper transcriptional factor ATF-like 3 isoform X1 [KO:K09034 ]
101434120 BATF; basic leucine zipper transcriptional factor ATF-like [KO:K09034 ]
101412450 CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452 ]
101425248 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
101417876 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
101435854 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101420075 PPP3CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
101427629 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
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 dnm04620 Toll-like receptor signaling pathway
dnm04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
