Entry Name PD-L1 expression and PD-1 checkpoint pathway in cancer - Pteropus vampyrus (large flying fox)
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 pvp05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Organism Pteropus vampyrus (large flying fox) [GN:
pvp ]
Gene 105288852 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105289309 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
105292939 EML4; echinoderm microtubule-associated protein-like 4 isoform X1 [KO:K15420 ]
105293029 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105293031 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105293045 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
105295015 BATF3; basic leucine zipper transcriptional factor ATF-like 3 isoform X2 [KO:K09034 ]
105295639 MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
105296040 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
105296533 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105296605 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105296799 TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403 ]
105297869 BATF2; basic leucine zipper transcriptional factor ATF-like 2 isoform X1 [KO:K09034 ]
105298423 CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470 ]
105299211 BATF; basic leucine zipper transcriptional factor ATF-like [KO:K09034 ]
105299371 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
105303020 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
105304587 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
105305747 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
105306294 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
105307215 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105307575 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105308956 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
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 pvp04514 Cell adhesion molecule (CAM) interaction
pvp04620 Toll-like receptor signaling pathway
pvp04660 T cell receptor signaling pathway
KO pathway
