Affinage

CD274

Programmed cell death 1 ligand 1 · UniProt Q9NZQ7

Round 2 corrected
Length
290 aa
Mass
33.3 kDa
Annotated
2026-04-28
130 papers in source corpus 41 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD274 (PD-L1/B7-H1) is a type I transmembrane glycoprotein of the B7 family that serves as the principal ligand for the PD-1 inhibitory receptor, suppressing T-cell proliferation, cytokine secretion, and anti-tumor immunity, while also functioning as a bidirectional signaling receptor that confers apoptosis resistance on cancer cells and, upon nuclear translocation under hypoxia, drives GSDMC transcription to switch TNF-α-induced apoptosis to pyroptosis (PMID:11015443, PMID:18223165, PMID:32929201). Surface PD-L1 protein abundance is governed by multiple post-translational mechanisms: N-glycosylation antagonizes GSK3β–β-TrCP-mediated proteasomal degradation, CMTM6/CMTM4 protect PD-L1 from lysosomal degradation in recycling endosomes, cyclin D–CDK4 promotes SPOP–Cullin 3-dependent ubiquitination, TNF-α–NF-κB–CSN5 signaling stabilizes PD-L1 by blocking ubiquitination, and SGLT2 shields PD-L1 from Cullin 3–SPOP recognition at the plasma membrane (PMID:27572267, PMID:28813410, PMID:29160310, PMID:27866850, PMID:36594471). Transcription of PD-L1 is principally induced through the IFN-γ–JAK1/JAK2–STAT1–IRF1 axis and further regulated by NF-κB, MYC, and YAP–TEAD, while translational output is controlled by an inhibitory 5′-UTR upstream open reading frame attenuated by eEF2K (PMID:28494868, PMID:26966191, PMID:33094805). Beyond canonical T-cell checkpoint function, PD-L1 on exosomes mediates systemic immunosuppression, on intestinal epithelium regulates innate mucosal immunity independently of adaptive lymphocytes, and on macrophage phagosomes directly recognizes the yeast surface protein Rpl20b to cross-regulate IL-10 production (PMID:30089911, PMID:24529703, PMID:38839956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 High

    Identification of B7-H1 as a novel B7-family member that co-stimulates T cells and preferentially induces IL-10 established CD274 as an immune-regulatory ligand distinct from known B7 molecules.

    Evidence Protein cloning, binding exclusion assays for CD28/CTLA-4/ICOS, T-cell co-stimulation assays

    PMID:10581077

    Open questions at the time
    • Counter-receptor identity unknown at this stage
    • In vivo relevance not yet tested
  2. 2000 High

    Discovery that PD-L1 is the functional ligand for PD-1 and that this interaction inhibits TCR-driven proliferation and cytokine secretion resolved the receptor identity and established the immunoinhibitory axis.

    Evidence Receptor-ligand binding assays, T-cell proliferation and cytokine assays, PD-1-deficient mice

    PMID:11015443

    Open questions at the time
    • Downstream signaling intermediates in T cells not mapped
    • Contribution of other PD-L1 receptors unclear
  3. 2002 High

    Demonstration that tumor-expressed PD-L1 induces apoptosis of activated T cells partly through a non-PD-1 receptor linked tumor immune evasion to PD-L1 and revealed additional receptor engagement beyond PD-1.

    Evidence T-cell apoptosis assays with tumor cells, IFN-γ-induced PD-L1 upregulation, in vivo P815 tumor model

    PMID:12091876

    Open questions at the time
    • Identity of the non-PD-1 receptor mediating apoptosis not determined
    • Mechanism of apoptosis induction not resolved
  4. 2003 High

    Evidence that PD-L1 on T cells and dendritic cells acts as a bidirectional signaling molecule — receiving reverse signals that co-stimulate then induce programmed death — expanded PD-L1 from a simple ligand to a signal-competent receptor.

    Evidence Immobilized anti-B7-H1 and PD-1-Ig co-stimulation, proliferation, cytokine, and caspase-3 apoptosis assays on T cells; MDC blockade experiments in ovarian carcinoma and NOD-SCID mice

    PMID:12569162 PMID:12704383

    Open questions at the time
    • Intracellular signaling domains and adaptors of reverse signaling not identified
    • In vivo validation of reverse signaling limited
  5. 2004 High

    B7-H1 knockout mice revealed a tissue-specific, non-redundant role in regulating intrahepatic CD8+ T-cell accumulation and deletion, demonstrating organ-level immune tolerance functions.

    Evidence B7-H1 gene-targeted KO mice, autoimmune hepatitis model, liver histology, flow cytometry

    PMID:15030776

    Open questions at the time
    • Whether hepatic PD-L1 acts via PD-1 or alternative receptor in vivo not resolved
    • Mechanism linking PD-L1 to CD8+ contraction-phase apoptosis undefined
  6. 2005 Medium

    Mapping of the PD-L1 promoter revealed NF-κB as a direct transcriptional activator downstream of IFN-γ via ERK1/2 and PI3K, providing the first cis-regulatory element governing PD-L1 induction.

    Evidence Luciferase reporter assays, EMSA, PI3K/ERK inhibitors in dermal fibroblasts

    PMID:16085391

    Open questions at the time
    • Relative contribution of NF-κB versus other IFN-γ-responsive elements not compared
    • Single cell type studied
  7. 2008 High

    Signaling-crippled PD-L1 mutants demonstrated that PD-L1 intrinsic signaling in cancer cells confers resistance to T-cell killing and Fas-mediated apoptosis, separating its cell-autonomous survival function from its role as a PD-1 ligand.

    Evidence Signaling-dead B7-H1 constructs, T-cell cytotoxicity, Fas ligation, staurosporine treatment

    PMID:18223165

    Open questions at the time
    • Specific cytoplasmic signaling partners not identified
    • Structural basis of intracellular signaling unknown
  8. 2012 High

    Spatial colocalization of PD-L1 with TILs in melanoma and dependence on local IFN-γ established the adaptive immune resistance paradigm, showing that tumors upregulate PD-L1 in direct response to T-cell attack.

    Evidence Large-cohort IHC of melanocytic lesions, IFN-γ detection, geographic correlation

    PMID:22461641

    Open questions at the time
    • Quantitative threshold of IFN-γ for PD-L1 induction not defined
    • Contribution of other cytokines at the interface not excluded
  9. 2016 High

    Elucidation of PD-L1 N-glycosylation as a stabilizing modification that blocks GSK3β–β-TrCP-mediated proteasomal degradation, with EGF/EGFR signaling inactivating GSK3β, revealed the first post-translational stability mechanism for PD-L1.

    Evidence N-glycosylation site mutagenesis, Co-IP of GSK3β–PD-L1 and β-TrCP–PD-L1, ubiquitination assays, gefitinib treatment, syngeneic mouse models

    PMID:27572267

    Open questions at the time
    • Glycosylation-independent stabilization routes not explored
    • Relative contribution of each glycosylation site in different tumor types uncertain
  10. 2016 High

    Identification of MYC as a direct transcriptional activator of PD-L1 connected oncogene-driven transcription to immune evasion, showing that MYC inactivation restores anti-tumor immunity through PD-L1 down-regulation.

    Evidence ChIP of MYC at Pd-l1 promoter, conditional MYC inactivation, enforced PD-L1 rescue, in vivo tumor models

    PMID:26966191

    Open questions at the time
    • Cooperativity between MYC and IFN-γ–IRF1 axis not defined
    • Whether MYC regulation is direct in all tumor types unclear
  11. 2016 High

    TNF-α–NF-κB–CSN5 axis was shown to stabilize PD-L1 by deubiquitination via CSN5 (COP9 signalosome subunit 5), adding a TNF-α-driven post-translational stabilization layer.

    Evidence CSN5 knockdown/overexpression, Co-IP, ubiquitination assays, half-life measurement, curcumin treatment, anti-CTLA-4 combination in vivo

    PMID:27866850

    Open questions at the time
    • Whether CSN5 acts through its metalloprotease (deneddylation) activity on cullin-RING ligases or independently is unclear
    • Relationship to GSK3β–β-TrCP pathway not integrated
  12. 2017 High

    Comprehensive genetic dissection established the IFN-γ–JAK1/JAK2–STAT1–IRF1 axis as the primary transcriptional pathway for PD-L1, with IRF1 directly binding the PD-L1 promoter, clarifying earlier NF-κB and STAT3 contributions as secondary.

    Evidence JAK/STAT/IRF1 genetic knockouts and knockdowns, ChIP for IRF1 at PD-L1 promoter, IFN-β/γ stimulation

    PMID:28494868

    Open questions at the time
    • Epigenetic modulation of IRF1 binding not characterized
    • Contribution of IRF1-independent IFN-γ signals at the PD-L1 locus unclear
  13. 2017 High

    A genome-wide haploid screen identified CMTM6 (and redundantly CMTM4) as essential for PD-L1 surface stability by binding PD-L1 in recycling endosomes and preventing lysosomal routing, revealing a non-ubiquitin-mediated stability mechanism complementary to proteasomal regulation.

    Evidence Haploid genetic screen, Co-IP/pulldown, ubiquitination and half-life assays, lysosomal inhibitors, plasma membrane proteomics, T-cell suppression assays

    PMID:28813410 PMID:28813417

    Open questions at the time
    • Structural basis of CMTM6–PD-L1 interaction unknown
    • Whether CMTM6 regulation extends to PD-L2 or other B7 ligands not resolved
  14. 2017 High

    Cyclin D–CDK4 phosphorylation of SPOP promotes Cullin 3–SPOP E3 ligase-mediated proteasomal degradation of PD-L1, linking cell-cycle machinery to immune evasion and providing a mechanistic rationale for CDK4/6 inhibitor–anti-PD-1 combination therapy.

    Evidence SPOP phosphorylation mutants, ubiquitination assays, Co-IP, CDK4/6 inhibitor treatment, FZR1/APC-mediated SPOP regulation, syngeneic mouse models with combination therapy

    PMID:29160310

    Open questions at the time
    • Cell-cycle phase-dependent dynamics of PD-L1 degradation not characterized in real time
    • Extent of SPOP mutation prevalence across tumor types as a PD-L1 modifier unclear
  15. 2018 High

    Discovery that tumor-derived exosomal PD-L1 suppresses CD8+ T-cell function systemically expanded the mechanism of PD-L1-mediated immune evasion beyond cell-surface interactions.

    Evidence Exosome isolation, flow cytometry, CD8+ T-cell functional assays, IFN-γ stimulation, in vivo tumor growth, clinical sample correlation

    PMID:30089911

    Open questions at the time
    • Relative contribution of exosomal vs. cell-surface PD-L1 to immune suppression in patients not quantified
    • Mechanism of PD-L1 sorting into exosomes not defined
  16. 2020 High

    Nuclear PD-L1, translocated via p-STAT3 interaction under hypoxia, directly activates GSDMC transcription, enabling caspase-8-mediated GSDMC cleavage and switching TNF-α responses from apoptosis to pyroptosis — a fundamentally new non-immune function for PD-L1.

    Evidence Co-IP of p-STAT3/PD-L1, nuclear fractionation, ChIP at GSDMC promoter, caspase-8 cleavage assays, pyroptosis assays, in vivo tumor necrosis in KO cells

    PMID:32929201

    Open questions at the time
    • Full spectrum of nuclear PD-L1 transcriptional targets unknown
    • Whether nuclear PD-L1 function occurs in non-cancer cells not tested
  17. 2020 High

    eEF2K was shown to promote PD-L1 translation by attenuating an inhibitory 5′-UTR upstream open reading frame, adding a translational regulatory layer to PD-L1 expression control.

    Evidence Polyribosome profiling, 5′-UTR reporter assays with uORF mutations, eEF2K knockdown/KO, NK cell cytotoxicity assays

    PMID:33094805

    Open questions at the time
    • Identity of the trans-acting factors recognizing the uORF CUG codon not determined
    • Whether other elongation factors contribute not tested
  18. 2022 High

    eEF2K was found to additionally stabilize PD-L1 post-translationally by phosphorylating GSK3β at S9, inactivating it and blocking PD-L1 degradation — revealing a dual translational and post-translational role for a single kinase.

    Evidence IP-MS identifying eEF2K–GSK3β interaction, in vitro kinase assay, Co-IP, eEF2K knockdown in mouse melanoma model, patient tumor IHC correlation

    PMID:35347072

    Open questions at the time
    • Whether eEF2K phosphorylation of GSK3β is specific to PD-L1 or affects other GSK3β substrates globally not determined
  19. 2023 High

    SGLT2 was identified as a plasma membrane partner that physically shields PD-L1 from Cullin 3–SPOP-mediated ubiquitination, and the SGLT2 inhibitor canagliflozin disrupts this interaction to degrade PD-L1, integrating metabolic transporter biology with immune checkpoint regulation.

    Evidence Co-IP of SGLT2–PD-L1, colocalization at plasma membrane and recycling endosomes, ubiquitination assays, Cullin3–SPOP interaction, siRNA, humanized mouse models

    PMID:36594471

    Open questions at the time
    • Whether SGLT2 transport function is coupled to PD-L1 protection not resolved
    • Generalizability to non-renal tumors uncertain
  20. 2024 High

    Phagosomal PD-L1 on macrophages was discovered to directly bind the yeast surface protein Rpl20b, cross-regulating IL-10 via innate immune receptor signaling — establishing PD-L1 as a pattern-recognition-like receptor for fungi, independent of adaptive immunity.

    Evidence Proximity labeling of phagosomal contents, comparative yeast vs. bacteria proteomics, yeast surface display library screen identifying Rpl20b, direct binding assays, auxin-inducible PD-L1 depletion, cytokine measurement

    PMID:38839956

    Open questions at the time
    • Whether PD-L1 recognizes other fungal species or additional ligands beyond Rpl20b is unknown
    • Structural basis of PD-L1–Rpl20b interaction not determined
    • In vivo relevance for antifungal immunity not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full repertoire of nuclear PD-L1 transcriptional targets, the structural basis of PD-L1 reverse signaling and its cytoplasmic adaptors, quantitative integration of the multiple ubiquitin-dependent and -independent degradation pathways, and the physiological significance of PD-L1's innate fungal recognition function in vivo.
  • Cytoplasmic signaling adaptors for PD-L1 reverse signaling remain unidentified
  • Comprehensive nuclear PD-L1 cistrome or interactome not generated
  • No integrated kinetic model of competing PD-L1 stabilization/degradation pathways exists

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0140110 transcription regulator activity 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 2 GO:0005768 endosome 2 GO:0005634 nucleus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 8 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9612973 Autophagy 2
Partners
CMTM4CMTM6CSN5EEF2KGSK3BPDCD1SGLT2SPOP

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 B7-H1 (CD274) was identified as a third member of the B7 family that does not bind CD28, CTLA-4, or ICOS, but co-stimulates T-cell proliferation and preferentially induces IL-10 secretion; IL-2 was required for the co-stimulatory effect. Protein cloning, binding assays, T-cell co-stimulation assays in vitro Nature medicine High 10581077
2000 PD-L1 (CD274) was identified as a ligand for the PD-1 immunoinhibitory receptor; engagement of PD-1 by PD-L1 inhibits TCR-mediated lymphocyte proliferation and cytokine secretion, and PD-1 signaling can inhibit suboptimal CD28-mediated co-stimulation. Ligand identification by homology/binding assays, T-cell proliferation and cytokine secretion assays, PD-1-deficient mouse characterization The Journal of experimental medicine High 11015443
2001 B7-H1 preferentially co-stimulates CD4+ T cells independently of CD28, enhancing mixed lymphocyte responses and secretion of IL-10, IFN-γ, and GM-CSF but not IL-2 or IL-4; mouse B7-H1 shares 69% amino acid homology with human B7-H1 and is inducible on macrophages, T cells, and B cells. Mouse homologue cloning, in vitro T-cell co-stimulation assays, cytokine measurement, in vivo tumor experiments Blood High 11238124
2002 Tumor-associated B7-H1 (CD274) induces apoptosis of antigen-specific T cells via one or more receptors other than PD-1; IFN-γ upregulates B7-H1 on tumor cell surface; B7-H1 expression on mouse P815 tumor cells promotes growth of immunogenic tumors in vivo by increasing apoptosis of activated tumor-reactive T cells. Flow cytometry, T-cell apoptosis assays in vitro, in vivo mouse tumor models, IFN-γ stimulation experiments Nature medicine High 12091876
2003 B7-H1 on activated human CD4+, CD8+, and CD45RO+ T cells can act as a bidirectional signaling molecule: engagement by immobilized anti-B7-H1 mAb or PD-1-Ig co-stimulates CD4+ T-cell proliferation and IL-10 secretion, subsequently leading to programmed cell death via upregulated TRAIL and caspase-3 activation. Cell surface expression analysis, immobilized antibody co-stimulation assays, proliferation assays, cytokine ELISA, apoptosis assays with caspase-3 activation The Journal of clinical investigation High 12569162
2003 B7-H1 expressed on myeloid dendritic cells (MDCs) in the tumor microenvironment downregulates T-cell immunity; blockade of B7-H1 on MDCs enhanced T-cell activation, shifted cytokine production from IL-10 toward IL-2 and IFN-γ, and improved T-cell-mediated anti-tumor activity in NOD-SCID mice. Flow cytometry, MDC isolation from ovarian carcinoma tissues, T-cell activation assays, cytokine measurement, in vivo NOD-SCID mouse experiments Nature medicine High 12704383
2004 B7-H1-deficient mice show spontaneous accumulation of CD8+ T cells in the liver while CD4+ T cell levels remain normal; antigen-driven CD8+ T cell apoptosis during the contraction phase is selectively impaired in the liver, leading to accelerated hepatocyte damage in experimental autoimmune hepatitis. B7-H1 thus selectively regulates accumulation and deletion of intrahepatic CD8+ T cells. Gene-targeted B7-H1 knockout mice, flow cytometry, experimental autoimmune hepatitis model, liver histology Immunity High 15030776
2005 IFN-γ induces B7-H1 mRNA and protein expression in dermal fibroblasts via NF-κB binding to the B7-H1 promoter, mediated by transient phosphorylation of ERK1/2 and PI3K; specific destruction of the NF-κB binding site abolished promoter activity. RT-PCR, luciferase reporter assays with B7-H1 promoter constructs, Western blot, EMSA, PI3K/ERK inhibitor experiments Journal of dermatological science Medium 16085391
2005 CD274 (B7-H1/PD-L1) expression in placental trophoblasts is regulated by oxygen concentration: expression is low in the first trimester and rises with increasing oxygen tension at onset of maternal blood flow; downregulation of CD274 mRNA by low oxygen occurs within 4-12 hours. Immunoblot analysis of placental lysates, culture of trophoblast cells under varying oxygen concentrations, mRNA analysis Biology of reproduction Medium 16251499
2008 B7-H1 on cancer cells functions as a receptor: when PD-1 on T cells engages B7-H1 on cancer cells, B7-H1 delivers an intracellular signal conferring resistance to T-cell killing, Fas-mediated apoptosis, and staurosporine-induced apoptosis; crippling B7-H1 signaling capacity (but not PD-1) ablates this resistance. Signaling-crippled B7-H1 mutant constructs, T-cell cytotoxicity assays, Fas ligation apoptosis assays, staurosporine treatment, cancer cell line experiments Blood High 18223165
2010 Human PD-L1 crystallizes with two molecules per asymmetric unit, suggesting a potential dimeric state; comparison with other B7 family structures revealed intrinsic factors involved in the interaction of the two PD-L1 molecules. X-ray crystallography (space group C222(1)) Protein & cell Medium 21203985
2010 Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by downregulating microRNA-513, which normally suppresses B7-H1 through its 3' UTR; overexpression of miR-513 inhibits C. parvum-induced B7-H1 protein expression and partially blocks T-cell apoptosis in co-culture. RT-PCR, miRNA transfection/overexpression, 3'UTR reporter assays, T-cell apoptosis co-culture assays, neutralizing antibody experiments The Journal of infectious diseases High 19916867
2010 Skin-specific overexpression of B7-H1 in transgenic mice promotes epithelial-mesenchymal transition (EMT) via constitutive reduction of E-cadherin and elevated expression of Slug and Twist transcription factors, accelerating chemically induced squamous cell carcinoma; inflammatory responses were inhibited in B7-H1 transgenic mice. B7-H1 transgenic mice (keratin 14 promoter), MCA-induced SCC model, TPA treatment, antibody blockade of B7-H1 and PD-1, E-cadherin/Slug/Twist expression analysis Cancer research High 21159661
2010 Keratinocyte-expressed B7-H1 (K14-B7-H1 transgenic mice) directly downregulates effector CD8+ T-cell function at local inflammatory sites via association with PD-1; IFN-γ production by presensitized CD8+ T cells stimulated with hapten-pulsed keratinocytes was markedly impaired and restored by anti-B7-H1 mAb. K14-B7-H1 transgenic mice, contact hypersensitivity model, adoptive transfer experiments, CD8+ T-cell co-culture with keratinocytes, cytokine measurement Journal of immunology High 20363965
2011 Upregulation of B7-H1 in hepatocellular carcinoma cells co-cultured with macrophages in a transwell system occurs at both mRNA and protein levels and is inhibited by blocking NF-κB or STAT3 signaling pathways, implicating macrophage-driven inflammatory microenvironment in B7-H1 induction. Transwell co-culture, Western blot, RT-PCR, NF-κB/STAT3 pathway inhibitors Cancer immunology, immunotherapy Medium 21853301
2012 B7-H1 (PD-L1) expression on melanocytes is strongly associated with and geographically colocalized with tumor-infiltrating lymphocytes; IFN-γ from TILs at the tumor interface drives B7-H1 expression, establishing an adaptive immune resistance mechanism where TILs trigger their own inhibition. Immunohistochemistry of human melanocytic lesions, IFN-γ detection, correlation analysis of B7-H1 and TIL colocalization Science translational medicine High 22461641
2014 B7-H1 (PD-L1) expressed on intestinal parenchymal cells (not hematopoietic cells) controls intestinal inflammation in an adaptive immunity-independent manner by inhibiting TNF-α production and stimulating IL-22 secretion from CD11c+CD11b+ lamina propria cells; B7-H1-deficient mice are highly susceptible to DSS- and TNBS-induced gut injury. B7-H1 knockout mice, bone marrow chimeric mice, DSS/TNBS colitis models, cytokine measurement, flow cytometry Cell reports High 24529703
2014 PTEN loss leads to increased cell-surface PD-L1 expression via PI3K pathway activation; PI3K pathway inhibition (AKT inhibitor MK-2206 or rapamycin) decreases PD-L1 expression; increased PD-L1 expression due to PTEN loss leads to decreased T-cell proliferation and increased T-cell apoptosis in co-culture. PTEN shRNA knockdown stable cell lines, flow cytometry, PI3K inhibitor treatment, co-culture T-cell assays Cancer immunology research High 24764583
2016 MYC transcription factor directly binds to the promoters of the Cd47 and Pd-l1 genes and regulates their expression; MYC inactivation in mouse tumors down-regulates PD-L1 expression and enhances the antitumor immune response; enforced expression of PD-L1 upon MYC inactivation suppresses the immune response and allows tumor growth. ChIP demonstrating MYC binding to Pd-l1 promoter, conditional MYC inactivation in mouse tumors, enforced PD-L1 expression rescue experiments, in vivo tumor growth assays Science High 26966191
2016 PD-L1 N-glycosylation (at N192, N200, N219) antagonizes GSK3β binding, preventing phosphorylation-dependent proteasome degradation of PD-L1 mediated by β-TrCP E3 ligase; EGF stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer; gefitinib destabilizes PD-L1 and enhances antitumor T-cell immunity. N-glycosylation site mutagenesis, Co-IP of GSK3β-PD-L1 and β-TrCP-PD-L1 complexes, ubiquitination assays, EGF/gefitinib treatment, syngeneic mouse models Nature communications High 27572267
2016 TNF-α triggers cancer cell immunosuppression via stabilization of PD-L1; NF-κB p65 induces COP9 signalosome 5 (CSN5), which inhibits ubiquitination and degradation of PD-L1; curcumin inhibits CSN5, diminishes PD-L1 expression, and sensitizes cancer cells to anti-CTLA4 therapy. NF-κB inhibition, Co-IP, ubiquitination assays, CSN5 knockdown/overexpression, PD-L1 half-life measurement, curcumin treatment, anti-CTLA4 combination experiments Cancer cell High 27866850
2017 The interferon-γ–JAK1/JAK2–STAT1/STAT2/STAT3–IRF1 axis primarily regulates PD-L1 expression; IRF1 directly binds to the PD-L1 promoter; PD-L2 is regulated by both IRF1 and STAT3 binding to its promoter. JAK/STAT/IRF1 genetic knockouts and knockdowns, ChIP demonstrating IRF1/STAT3 binding to PD-L1 promoter, IFN-β and IFN-γ stimulation experiments Cell reports High 28494868
2017 CMTM6 binds PD-L1 at the plasma membrane and in recycling endosomes, reducing PD-L1 ubiquitination and increasing its protein half-life; CMTM6 prevents PD-L1 from lysosome-mediated degradation; CMTM4 shares this function but other CMTM family members do not; CMTM6 depletion reduces PD-L1 without affecting MHC class I surface expression. Haploid genetic screen, Co-IP/pulldown demonstrating CMTM6-PD-L1 association, ubiquitination assays, half-life measurement, lysosomal inhibitor experiments, quantitative plasma membrane proteome profiling, T-cell suppression assays in vitro and in vivo Nature High 28813410 28813417
2017 MiR-152 directly binds to the B7-H1 (CD274) 3' UTR in gastric cancer cells and inhibits B7-H1 expression; elevation of miR-152 enhances T-cell proliferation and effector cytokine production via suppression of the B7-H1/PD-1 pathway. miR-152 mimic/inhibitor transfection, 3'UTR luciferase reporter assay, Western blot, T-cell co-culture functional assays Oncotarget Medium 28427226
2017 YAP regulates PD-L1 transcription in NSCLC cells; ChIP assays demonstrated YAP binding to the PD-L1 enhancer region encompassing two putative TEAD binding sites; YAP knockdown decreases PD-L1 mRNA and protein, and YAP overexpression rescues PD-L1 levels. siRNA knockdown, overexpression, ChIP with YAP-specific antibody, luciferase reporter, protein/mRNA analysis Oncotarget Medium 29383103
2017 Cyclin D-CDK4 destabilizes PD-L1 via cullin 3-SPOP E3 ligase-mediated proteasome degradation; CDK4/6 inhibition increases PD-L1 protein by impeding CDK4-mediated SPOP phosphorylation, promoting SPOP degradation by FZR1/APC; SPOP loss-of-function mutations increase PD-L1 levels and reduce tumor-infiltrating lymphocytes; CDK4/6 inhibitor + anti-PD-1 combination markedly improves survival in mouse models. CDK4/6 inhibitor treatment, SPOP phosphorylation mutant constructs, ubiquitination assays, Co-IP, KO mouse models, primary human prostate cancer specimens, in vivo combination therapy Nature High 29160310
2017 Small-molecule Sigma1 (SIGMAR1) inhibition induces selective autophagic degradation of PD-L1 distinct from bulk macroautophagy or general ER stress-associated autophagy; Sigma1 activators increase PD-L1 cell surface expression; Sigma1 inhibitor suppresses IFN-γ-induced PD-L1 and reduces functional PD-1/PD-L1 interaction in T-cell/cancer cell co-culture. Sigma1 RNAi knockdown, pharmacological Sigma1 activator/inhibitor competition, autophagy inhibitor experiments, flow cytometry, T-cell/cancer cell co-culture Molecular cancer research Medium 29117944
2018 A secreted splice variant of PD-L1 (secPD-L1) that lacks the transmembrane domain contains a unique 18 amino acid tail with a cysteine enabling homodimerization; recombinant secPD-L1 dimerizes and inhibits T-cell proliferation and IFN-γ production in vitro more effectively than monomeric soluble PD-L1; it is preferentially expressed in activated myeloid cells. Splice variant cloning and characterization, recombinant protein production, dimerization assays, T-cell proliferation and IFN-γ assays in vitro, transcriptomic analysis (TCGA) Cancer immunology, immunotherapy Medium 30564891
2018 PD-L1 delivers intrinsic intracellular signals in cancer cells that enhance cancer cell survival, regulate stress responses, and confer resistance to pro-apoptotic stimuli including interferons; these functions are independent of its role as a T-cell inhibitory ligand. Review synthesizing evidence from PD-L1 signalosome studies including co-immunoprecipitation and pathway analysis Signal transduction and targeted therapy Low 30275987
2018 HDAC1 and HDAC3 are required for IFN-γ-induced B7-H1 expression in gastric cancer cells; HDAC inhibitors suppress IFN-γ signaling by reducing JAK2, p-JAK1, p-JAK2, p-STAT1, preventing STAT1 nuclear translocation, and reducing H3K9 acetylation at the B7-H1 gene promoter. HDAC inhibitor treatment, HDAC1/3 siRNA knockdown, Western blot, nuclear fractionation, ChIP for H3K9 acetylation, in vivo mouse GC model Clinical epigenetics Medium 30537988
2018 EphA10 receptor mediates cell contact-dependent (juxtacrine) signaling that upregulates PD-L1 expression on tumor cells; EphA10 knockout in tumor cells increased T-cell-mediated antitumor immunity in syngeneic mouse models; EphA10 expression positively correlates with PD-L1 in human breast tumor tissues. EphA10 KO in tumor cells, syngeneic mouse models, T-cell cytotoxicity assays, IHC correlation in human breast tumors Cancer research Medium 29789418
2018 B7-H1 expression on dendritic cells protects DCs from CTL-mediated lysis, thereby maintaining polyclonal (subdominant) CTL responses; loss of B7-H1 on DCs paradoxically suppresses CTL responses to subdominant antigens while enhancing responses to dominant antigens, facilitating tumor escape of subdominant antigen variants. B7-H1-deficient DC immunization experiments, multi-antigen-loaded DC models, in vivo mouse tumor models with dominant/subdominant antigen variants Proceedings of the National Academy of Sciences of the United States of America High 29507197
2018 Exosomal PD-L1 from melanoma tumor cells suppresses CD8+ T-cell function and facilitates tumor growth; IFN-γ stimulation increases PD-L1 on tumor-derived exosomes; circulating exosomal PD-L1 correlates with IFN-γ levels and stratifies clinical responders from non-responders in anti-PD-1 therapy. Exosome isolation and characterization, flow cytometry, CD8+ T-cell functional assays, IFN-γ stimulation, in vivo tumor growth experiments, clinical sample analysis Nature High 30089911
2019 Autophagy inhibition increases PD-L1 expression in gastric cancer via accumulation of p62/SQSTM1 and activation of NF-κB; p62/SQSTM1 knockdown or NF-κB inhibition attenuates PD-L1 induction upon autophagy blockade; IFN-γ-induced PD-L1 transcription is enhanced by autophagy inhibition. Pharmacological autophagy inhibitors, siRNA knockdown of autophagy genes/p62/NF-κB, Western blot, flow cytometry, xenograft experiments, patient tissue IHC Journal of experimental & clinical cancer research Medium 30925913
2020 Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation; nuclear PD-L1 enhances transcription of the gasdermin C (GSDMC) gene; GSDMC is cleaved by caspase-8 upon TNF-α treatment, generating an N-terminal domain that forms membrane pores and induces pyroptosis, switching TNF-α-induced apoptosis to pyroptosis in cancer cells. Co-IP of p-Stat3/PD-L1 complex, nuclear fractionation, ChIP for nuclear PD-L1 at GSDMC promoter, caspase-8 cleavage assays, pyroptosis assays, in vivo tumor necrosis experiments with KO cells Nature cell biology High 32929201
2020 eEF2K promotes PD-L1 translation by facilitating association of PD-L1 mRNA with translationally active polyribosomes; PD-L1 mRNA translation is regulated by an upstream open reading frame (uORF) in its 5'-UTR beginning with a non-canonical CUG codon, whose inhibitory effect is attenuated by eEF2K; eEF2K-depleted cancer cells are more vulnerable to NK cell-mediated immune attack. eEF2K knockdown/KO in prostate and lung cancer cells, polyribosome profiling, 5'-UTR reporter assays with uORF mutations, NK cell cytotoxicity assays The Biochemical journal High 33094805
2022 eEF2K directly binds to and inactivates GSK3β by phosphorylating it at serine 9 (S9), leading to PD-L1 protein stabilization and upregulation; eEF2K knockdown decreases PD-L1 expression and enhances CD8+ T-cell activity, attenuating tumor growth in vivo; p-GSK3β/S9 expression positively correlates with eEF2K and PD-L1 in melanoma. IP-MS identifying eEF2K-GSK3β interaction, in vitro kinase assays, Co-IP, phospho-specific antibodies, eEF2K knockdown mouse melanoma model, patient tumor analysis Journal for immunotherapy of cancer High 35347072
2022 PD-1/PD-L1 signaling on Tregs and CD80/PD-L1 signaling on Teffs regulate transendothelial migration across lymphatic endothelial cells (LECs); PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to upregulate VCAM-1 on LECs; CD80/PD-L1 signaling upregulates VCAM-1 through ERK and NFκB-p65. Antibody blockade of PD-1/PD-L1/CD80, in vitro transendothelial migration assays, pathway inhibitors (PI3K/Akt, ERK, NFκB), VE-cadherin junctional analysis, VCAM-1 expression, in vivo tumor draining lymph node experiments Nature communications Medium 35449134
2023 SGLT2 colocalizes with PD-L1 at the plasma membrane and recycling endosomes and protects PD-L1 from proteasome-mediated degradation; canagliflozin disrupts the SGLT2-PD-L1 physical interaction, allowing recognition of PD-L1 by Cullin3-SPOP E3 ligase, which triggers ubiquitination and proteasomal degradation of PD-L1. Colocalization studies, Co-IP of SGLT2-PD-L1, ubiquitination assays, Cullin3-SPOP interaction assays, SGLT2 siRNA knockdown, mouse and humanized immune models The Journal of clinical investigation High 36594471
2024 PD-L1 specifically enriches in phagosomes containing yeast (not bacteria) and directly binds to yeast; surface display library screening identified the yeast ribosomal protein Rpl20b as a fungal ligand for PD-L1; auxin-inducible PD-L1 depletion in macrophages demonstrated that PD-L1 detection of Rpl20b cross-regulates IL-10 production induced by other innate immune receptors. Proximity labeling of phagosomal contents (PhagoPL), comparative proteomics of phagosomes from yeast vs. bacteria, surface display library screening, direct binding assays, auxin-inducible depletion system, cytokine measurement Nature High 38839956

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 PD-1 and its ligands in tolerance and immunity. Annual review of immunology 4351 18173375
2000 Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of experimental medicine 4219 11015443
2002 Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature medicine 4064 12091876
2001 PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nature immunology 2346 11224527
2018 Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2247 30089911
1999 B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature medicine 2049 10581077
2014 Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 2008 24714771
2016 PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Science translational medicine 1999 26936508
2010 The PD-1 pathway in tolerance and autoimmunity. Immunological reviews 1859 20636820
2012 Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science translational medicine 1801 22461641
2017 Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Molecular cancer therapeutics 1779 28835386
2018 Regulation and Function of the PD-L1 Checkpoint. Immunity 1737 29562194
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell reports 1464 28494868
2013 Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Science translational medicine 1445 23986400
2007 Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America 1212 17360651
2015 Classifying Cancers Based on T-cell Infiltration and PD-L1. Cancer research 1197 25977340
2021 PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nature reviews. Clinical oncology 1189 33580222
2019 Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Molecular cancer 1144 30646912
2016 MYC regulates the antitumor immune response through CD47 and PD-L1. Science (New York, N.Y.) 1139 26966191
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2014 PD-L1 expression in triple-negative breast cancer. Cancer immunology research 1107 24764583
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nature medicine 1050 12704383
2010 Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 1037 20628145
2016 Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nature communications 925 27572267
2017 Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 849 29160310
2016 Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 827 28039262
2019 Mechanisms Controlling PD-L1 Expression in Cancer. Molecular cell 824 31668929
2017 PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. Clinical cancer research : an official journal of the American Association for Cancer Research 823 28167507
2014 Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nature communications 803 25348003
2003 Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. Journal of immunology (Baltimore, Md. : 1950) 775 12538684
2020 PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nature cell biology 774 32929201
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2017 CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature 751 28813417
2009 Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. The Journal of experimental medicine 728 19451266
2016 Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer. JAMA oncology 709 26562159
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2016 Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer cell 668 27866850
2017 Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 569 28813410
2019 Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. Journal of hematology & oncology 555 31488176
2008 B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood 430 18223165
2013 Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clinical cancer research : an official journal of the American Association for Cancer Research 380 23613317
2016 PD-L1 Expression in Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 373 27117833
2004 B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity 318 15030776
2020 Regulation of PD-L1 Expression by NF-κB in Cancer. Frontiers in immunology 298 33324403
2016 What does PD-L1 positive or negative mean? The Journal of experimental medicine 271 27903604
2017 PD-L1. Journal of clinical pathology 254 29097600
2017 Tumor-derived exosomes modulate PD-L1 expression in monocytes. Science immunology 250 28754746
2020 PD-L1 degradation pathway and immunotherapy for cancer. Cell death & disease 243 33159034
2018 The intracellular signalosome of PD-L1 in cancer cells. Signal transduction and targeted therapy 243 30275987
2001 B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood 172 11238124
2003 Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. The Journal of clinical investigation 170 12569162
2019 Autophagy inhibition enhances PD-L1 expression in gastric cancer. Journal of experimental & clinical cancer research : CR 144 30925913
2017 Comprehensive screening for PD-L1 expression in thyroid cancer. Endocrine-related cancer 141 28093480
2017 Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1. Molecular cancer research : MCR 139 29117944
2002 B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression. Blood 138 12468426
2008 Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer. Cancer letters 129 18486325
2011 Soluble B7-H1: differences in production between dendritic cells and T cells. Immunology letters 126 22138406
2018 A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression. Cancer immunology, immunotherapy : CII 115 30564891
2017 YAP regulates PD-L1 expression in human NSCLC cells. Oncotarget 113 29383103
2008 B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression. Journal of cancer research and clinical oncology 107 18347814
2005 IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells. Journal of dermatological science 104 16085391
2017 Imaging PD-L1 Expression with ImmunoPET. Bioconjugate chemistry 100 29125731
2022 Upregulation of PD-L1 in Senescence and Aging. Molecular and cellular biology 88 36154662
2010 B7-H1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin. Cancer research 88 21159661
2014 The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. Hematology/oncology and stem cell therapy 85 24398144
2019 Base excision repair regulates PD-L1 expression in cancer cells. Oncogene 82 30755733
2017 Comprehensive analysis of PD-L1 expression in glioblastoma multiforme. Oncotarget 82 28178682
2018 [Predictive value of PD-L1 diagnostics]. Der Pathologe 78 30367225
2011 Upregulation of B7-H1 expression is associated with macrophage infiltration in hepatocellular carcinomas. Cancer immunology, immunotherapy : CII 76 21853301
2023 PD-L1 testing by immunohistochemistry in immuno-oncology. Biomolecules & biomedicine 75 35964287
2017 Clinical applications of PD-L1 bioassays for cancer immunotherapy. Journal of hematology & oncology 74 28514966
2016 PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients. Oncoimmunology 72 28197377
2015 Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1. Oncotarget 71 26110571
2017 PD-L1 expression in extrahepatic cholangiocarcinoma. Histopathology 68 28419539
2023 Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling. The Journal of clinical investigation 67 36594471
2006 Immunoregulatory role of B7-H1 in chronicity of inflammatory responses. Cellular & molecular immunology 66 16893498
2024 PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders. Molecular therapy : the journal of the American Society of Gene Therapy 65 39342430
2018 Heterogeneity of PD-L1 Expression and Relationship with Biology of NSCLC. Anticancer research 63 29970498
2015 RAC1 P29S regulates PD-L1 expression in melanoma. Pigment cell & melanoma research 63 26176707
2014 Glial cells suppress postencephalitic CD8+ T lymphocytes through PD-L1. Glia 63 24890099
2010 A dimeric structure of PD-L1: functional units or evolutionary relics? Protein & cell 63 21203985
2023 PD-L1: expression regulation. Blood science (Baltimore, Md.) 62 37228770
2021 Optimized PD-L1 scoring of gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 60 33954872
2022 Soluble PD-L1 as an early marker of progressive disease on nivolumab. Journal for immunotherapy of cancer 59 35131863
2022 PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration. Nature communications 59 35449134
2017 CD70 and PD-L1 in anaplastic thyroid cancer - promising targets for immunotherapy. Histopathology 59 28383817
2019 Beyond PD-L1 Markers for Lung Cancer Immunotherapy. International journal of molecular sciences 57 31003463
2010 Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. The Journal of infectious diseases 57 19916867
2014 Tissue-expressed B7-H1 critically controls intestinal inflammation. Cell reports 56 24529703
2005 Trophoblast CD274 (B7-H1) is differentially expressed across gestation: influence of oxygen concentration. Biology of reproduction 55 16251499
2017 MicroRNA-152 regulates immune response via targeting B7-H1 in gastric carcinoma. Oncotarget 54 28427226
2018 Gene code CD274/PD-L1: from molecular basis toward cancer immunotherapy. Therapeutic advances in medical oncology 51 30574211
2014 PD-1 and PD-L1 antibodies for melanoma. Human vaccines & immunotherapeutics 51 25625924
2021 The role of exosomal PD-L1 in tumor immunotherapy. Translational oncology 47 33647542
2020 Cytology for PD-L1 testing: A systematic review. Lung cancer (Amsterdam, Netherlands) 47 32007657
2018 Efficient PD-L1 gene silence promoted by hyaluronidase for cancer immunotherapy. Journal of controlled release : official journal of the Controlled Release Society 47 30476528
2018 HDAC is indispensable for IFN-γ-induced B7-H1 expression in gastric cancer. Clinical epigenetics 45 30537988
2019 The expression of PD-L1 in salivary gland carcinomas. Scientific reports 44 31484986
2021 Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy. Journal of immunology research 42 33628854
2013 Overexpression of B7-H1 correlates with malignant cell proliferation in pancreatic cancer. Oncology reports 41 24378899
2022 eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma. Journal for immunotherapy of cancer 39 35347072
2021 Non-cytomembrane PD-L1: An atypical target for cancer. Pharmacological research 38 34174446
2005 Expression of B7-H1 in inflammatory renal tubular epithelial cells. Nephron. Experimental nephrology 38 16282703
2021 Emerging role of PD-L1 modification in cancer immunotherapy. American journal of cancer research 37 34522452
2016 CTC immune escape mediated by PD-L1. Medical hypotheses 37 27372873
2011 Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis. Cancer research 37 21730022
2015 Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. PloS one 36 25807464
2020 eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA. The Biochemical journal 35 33094805
2010 Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses. Journal of immunology (Baltimore, Md. : 1950) 35 20363965
2019 Glial Cell Expression of PD-L1. International journal of molecular sciences 34 30987269
2017 PD-L1 inhibitors in the pipeline: Promise and progress. Oncoimmunology 34 29296516
2015 B7-H1 enhances proliferation ability of gastric cancer stem-like cells as a receptor. Oncology letters 34 25789052
2022 Exosomal PD-L1 predicts response with immunotherapy in NSCLC patients. Clinical and experimental immunology 33 35514075
2006 Significance of B7-H1 overexpression in kidney cancer. Clinical genitourinary cancer 33 17239274
2020 Immune Escape Mediated by Exosomal PD-L1 in Cancer. Advanced biosystems 31 32383351
2022 Superinduction of immunosuppressive glioblastoma extracellular vesicles by IFN-γ through PD-L1 and IDO1. Neuro-oncology advances 30 35990703
2014 IL-12 regulates B7-H1 expression in ovarian cancer-associated macrophages by effects on NF-κB signalling. Asian Pacific journal of cancer prevention : APJCP 30 25081699
2024 Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor. Nature 29 38839956
2017 New Dancing Couple: PD-L1 and MicroRNA. Scandinavian journal of immunology 29 28675453
2020 Protein homodimer sequestration with small molecules: Focus on PD-L1. Biochemical pharmacology 28 31972166
2003 Immunology of B7-H1 and its roles in human diseases. International journal of hematology 28 14686489
2021 Expression of PD-L1 in EBV-associated malignancies. International immunopharmacology 26 33765613
2018 Juxtacrine Signaling Inhibits Antitumor Immunity by Upregulating PD-L1 Expression. Cancer research 26 29789418
2007 Porcine PD-L1: cloning, characterization, and implications during xenotransplantation. Xenotransplantation 26 17489864
2019 Design of PD-L1 inhibitors for lung cancer. Bioinformation 24 31435160
2018 B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proceedings of the National Academy of Sciences of the United States of America 24 29507197
2006 Immune accessory functions of human endothelial cells are modulated by overexpression of B7-H1 (PDL1). Human immunology 24 16916652
2023 Regulation of PD-L1 Trafficking from Synthesis to Degradation. Cancer immunology research 23 37290119