Entry Name PD-L1 expression and PD-1 checkpoint pathway in cancer - Equus asinus (ass)
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 eai05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Ortholog table Organism Equus asinus (ass) [GN:
eai ]
Gene 106848533 HIF1A; LOW QUALITY PROTEIN: hypoxia-inducible factor 1-alpha [KO:K08268 ]
106829795 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
106848305 EML4; echinoderm microtubule-associated protein-like 4 [KO:K15420 ]
106840141 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
106822593 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
106824993 PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
106838100 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
106829313 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
106836695 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
106825951 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
106828796 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
106826327 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
106834020 toll/interleukin-1 receptor domain-containing adapter protein isoform X2 [KO:K05403 ]
106825588 toll/interleukin-1 receptor domain-containing adapter protein-like [KO:K05403 ]
106834265 MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729 ]
106834926 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
106825560 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
106822461 NFATC3; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333 ]
106832333 TICAM1; LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 1 [KO:K05842 ]
106831473 LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 2 [KO:K05409 ]
106827194 BATF3; basic leucine zipper transcriptional factor ATF-like 3 [KO:K09034 ]
106833606 BATF2; basic leucine zipper transcriptional factor ATF-like 2 isoform X1 [KO:K09034 ]
106827698 BATF; basic leucine zipper transcriptional factor ATF-like [KO:K09034 ]
106840276 CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451 ]
106841549 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
106829097 LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
106834358 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
106847712 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348 ] [EC:3.1.3.16 ]
106834431 PPP3CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
106842388 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X3 [KO:K04348 ] [EC:3.1.3.16 ]
106828142 CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470 ]
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 eai04620 Toll-like receptor signaling pathway
eai04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
