Entry
Name
PD-L1 expression and PD-1 checkpoint pathway in cancer - Desmodus rotundus (common vampire bat)
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
dro05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Ortholog table
Organism
Desmodus rotundus (common vampire bat) [GN:
dro ]
Gene
112297965 EML4; echinoderm microtubule-associated protein-like 4 [KO:K15420 ]
112321016 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
112305224 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
112314466 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
112310002 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
112299448 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
112307667 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
112300474 CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467 ] [EC:2.7.11.10 ]
112317867 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
112307780 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
112298562 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
112301793 TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403 ]
112309628 MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
112322654 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
112303992 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
112300806 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
112317041 BATF2; basic leucine zipper transcriptional factor ATF-like 2 [KO:K09034 ]
112311864 BATF; basic leucine zipper transcriptional factor ATF-like [KO:K09034 ]
112296620 BATF3; basic leucine zipper transcriptional factor ATF-like 3 isoform X1 [KO:K09034 ]
112314382 CD3E; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 epsilon chain [KO:K06451 ]
112304844 LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362 ]
112303845 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
112305449 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
112317863 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
112305248 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma 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 pathway
dro04620 Toll-like receptor signaling pathway
dro04660 T cell receptor signaling pathway
KO pathway
LinkDB
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