Affinage

CD274

Programmed cell death 1 ligand 1 · UniProt Q9NZQ7

Length
290 aa
Mass
33.3 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD274 (PD-L1/B7-H1) is a B7-family transmembrane ligand that delivers coinhibitory signals to T cells, originally identified as a third B7 member that co-stimulates T-cell proliferation and IL-10 secretion without binding CD28, CTLA-4, or ICOS (PMID:10581077), and subsequently shown to bind PD-1 on activated lymphocytes to induce T-cell apoptosis and cell-cycle arrest while also engaging a PD-1-independent receptor (PMID:12091876, PMID:12721664). Beyond lymphocyte suppression, PD-L1 controls innate immune homeostasis: epithelial/parenchymal PD-L1 dampens intestinal inflammation by suppressing TNF-α and inducing IL-22 (PMID:24529703) and restrains innate clearance of corneal HSV-1 (PMID:29669784), and PD-L1 acts as a phagosomal innate sensor that directly binds the fungal ribosomal protein Rpl20b to cross-regulate IL-10 production (PMID:38839956). Its expression is driven transcriptionally by direct MYC promoter binding (PMID:26966191) and by NF-κB-dependent and JAK-STAT-dependent inputs from TNF-α, autophagy blockade, senescence, and a TRAF6–YAP1/TFCP2 axis (PMID:27866850, PMID:30925913, PMID:36154662, PMID:38583649), with the PI3K/AKT pathway elevating PD-L1 upon PTEN loss (PMID:24764583). Translation is gated by eEF2K relieving an inhibitory uORF in the PD-L1 5'-UTR (PMID:33094805). PD-L1 protein abundance is set post-translationally by competing ubiquitination machinery: CK2 phosphorylation at Thr285/Thr290 blocks the CUL3-SPOP adaptor (PMID:35385574), CMTM6/CMTM4 (PMID:28813410), CSN5 deubiquitination (PMID:27866850), and SGLT2 sequestration at the membrane and recycling endosomes (PMID:36594471) each stabilize PD-L1, while direct LC3 (MAP1LC3B) binding routes it to autophagic-lysosomal degradation (PMID:39710370). PD-L1 additionally exerts tumor-cell-intrinsic effects, promoting EMT in keratinocyte carcinogenesis (PMID:21730022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Established CD274 as a novel B7-family ligand distinct from known CD28-superfamily interactions, defining a previously unrecognized T-cell costimulatory axis.

    Evidence Receptor binding assays and T-cell co-stimulation with cytokine measurement

    PMID:10581077

    Open questions at the time
    • Receptor identity not resolved
    • Costimulation vs coinhibition not reconciled
  2. 2002 High

    Showed tumor PD-L1 drives antigen-specific T-cell apoptosis and IFN-γ-inducible surface expression, framing it as an immune-evasion mechanism and therapeutic target.

    Evidence In vitro T-cell apoptosis assays, mouse P815 tumor model, IHC on human tumors

    PMID:12091876

    Open questions at the time
    • Apoptotic receptor other than PD-1 not identified
    • Intracellular signaling not defined
  3. 2003 Medium

    Synthesized PD-1 as the inhibitory receptor for PD-L1 inducing apoptosis and cell-cycle arrest, while noting a distinct costimulatory receptor.

    Evidence Review of receptor binding and T-cell functional/apoptosis data

    PMID:12721664

    Open questions at the time
    • Review, not primary data
    • Second receptor unidentified
  4. 2005 Medium

    Linked PD-L1 expression to oxygen tension in trophoblasts, indicating environmental/microenvironmental control of CD274 during placental development.

    Evidence Placental lysate immunoblot and trophoblast culture under varying oxygen with mRNA quantification

    PMID:16251499

    Open questions at the time
    • Molecular oxygen-sensing pathway not mapped
    • Functional consequence for fetal tolerance not tested
  5. 2011 Medium

    Revealed a tumor-cell-intrinsic role beyond immune suppression: PD-L1 promotes EMT during squamous carcinogenesis.

    Evidence B7-H1 transgenic mouse chemical carcinogenesis with E-cadherin/Slug/Twist immunostaining

    PMID:21730022

    Open questions at the time
    • Intracellular signaling driving EMT not defined
    • Single transgenic model
  6. 2014 High

    Defined PI3K/AKT signaling (via PTEN loss) and parenchymal PD-L1 in tissue immune homeostasis as distinct regulatory and effector contexts.

    Evidence PTEN knockdown with PI3K inhibitors and co-culture; DSS/TNBS colitis in B7-H1 KO and bone marrow chimeras

    PMID:24529703 PMID:24764583

    Open questions at the time
    • Direct transcription factor downstream of AKT not pinned
    • Mechanism of IL-22 induction unresolved
  7. 2016 High

    Identified direct transcriptional (MYC) and post-translational deubiquitination (CSN5/NF-κB) control of PD-L1, separating its induction from its protein stability.

    Evidence MYC ChIP and genetic inactivation/rescue in mouse tumors; reciprocal Co-IP and ubiquitination assays for CSN5 with curcumin

    PMID:26966191 PMID:27866850

    Open questions at the time
    • Cooperation of MYC with other TFs unclear
    • CSN5 specificity vs other DUBs not addressed
  8. 2017 High

    Established CMTM6/CMTM4 as surface partners that protect PD-L1 from ubiquitination, and an exosomal hY4/TLR7 route inducing PD-L1 in monocytes, defining stability and trans-cellular induction mechanisms.

    Evidence Haploid genetic screen, Co-IP, half-life assays (CMTM6); CLL exosome/hY4 transfer to TLR7-KO monocytes

    PMID:28754746 PMID:28813410

    Open questions at the time
    • E3 ligase opposed by CMTM6 not fully resolved here
    • TLR7 downstream effectors driving PD-L1 not detailed
  9. 2018 High

    Demonstrated constitutive corneal PD-L1 restrains innate antiviral clearance, extending PD-L1 function to non-hematopoietic innate immune regulation.

    Evidence B7-H1 KO mice, local antibody blockade, bone marrow chimeras, HSV-1 titer measurement

    PMID:29669784

    Open questions at the time
    • Receptor on innate cells unidentified
    • Signaling for chemokine suppression unclear
  10. 2019 Medium

    Extended PD-L1 biology to autophagy-coupled NF-κB induction, constitutive nonclassical monocyte expression, and a tumor-intrinsic survival signalosome.

    Evidence Autophagy inhibition with p62/NF-κB knockdowns; two-photon imaging of NCMs; mechanistic review of intracellular signaling

    PMID:30275987 PMID:30925913 PMID:31227596

    Open questions at the time
    • Intracellular-domain signaling partners not biochemically defined (review)
    • NCM PD-L1 receptor engagement unmapped
  11. 2020 High

    Identified translational control of PD-L1 via eEF2K relieving a uORF, adding a layer between mRNA abundance and protein output.

    Evidence eEF2K knockdown/KO, polyribosome profiling, uORF reporter and NK cytotoxicity assays

    PMID:33094805

    Open questions at the time
    • Signals controlling eEF2K activity on this uORF not defined
    • Generality across cell types untested
  12. 2022 High

    Resolved competing stability switches and a transendothelial migration function: CK2 phosphorylation blocks SPOP-mediated degradation, senescence/JAK-STAT induces PD-L1, and PD-1/PD-L1 signals through PI3K/Akt-ERK-NFκB in lymphatic endothelium.

    Evidence Kinase/mutagenesis/ubiquitination assays (CK2); senescence conditioned media with JAK-STAT inhibition; transendothelial migration assays with pathway inhibitors

    PMID:35385574 PMID:35449134 PMID:36154662

    Open questions at the time
    • Upstream control of CK2 at PD-L1 unclear
    • LEC junctional signaling directionality incompletely mapped
  13. 2023 High

    Defined SGLT2 as a membrane/recycling-endosome partner shielding PD-L1 from CUL3-SPOP, providing a metabolically targetable stability mechanism.

    Evidence Co-localization imaging, Co-IP, ubiquitination assays, SGLT2 silencing, canagliflozin in syngeneic/humanized mice

    PMID:36594471

    Open questions at the time
    • Whether SGLT2 transport activity is required not separated from binding
    • Tissue specificity of this axis unclear
  14. 2024 Medium

    Established new degradation and innate-sensing functions: direct LC3 binding routes PD-L1 to autophagy-lysosome, TRAF6-YAP1/TFCP2 drives transcription, and PD-L1 acts as a phagosomal fungal sensor binding Rpl20b.

    Evidence Co-IP/BiFC/MST/SPR autophagy assays; CRISPRi and K63-ubiquitination assays; PhagoPL proximity labeling and surface display screen with auxin-inducible depletion

    PMID:38583649 PMID:38839956 PMID:39710370

    Open questions at the time
    • Physiological trigger for LC3-mediated turnover unclear
    • Signaling output of Rpl20b sensing beyond IL-10 cross-regulation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intracellular signaling machinery that transduces PD-L1's tumor-cell-intrinsic survival and innate-sensing signals, and the identity of the non-PD-1 costimulatory/apoptotic receptor, remain unresolved.
  • No biochemically defined intracellular-domain effectors
  • Second receptor still unidentified
  • Integration of competing stability pathways in vivo unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
CMTM4CMTM6CSN5MAP1LC3BPDCD1SGLT2SPOP

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 B7-H1 (CD274/PD-L1) was identified as a third B7 family member 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 this co-stimulatory effect. Receptor binding assays (negative for CD28/CTLA-4/ICOS), T-cell co-stimulation assays with polyclonal and allogeneic stimuli, cytokine measurement Nature medicine High 10581077
2002 Tumor-associated B7-H1 (PD-L1) promotes apoptosis of antigen-specific T cells in vitro and in vivo, increasing growth of immunogenic tumors; IFN-γ upregulates B7-H1 on tumor cell surfaces; the apoptotic effect is mediated largely by receptor(s) other than PD-1. In vitro T-cell apoptosis assays with human T-cell clones, mouse P815 tumor model in vivo, immunohistochemistry on human tumor tissues, flow cytometry Nature medicine High 12091876
2003 B7-H1 binds PD-1 on activated T and B cells, inhibiting T-cell responses by inducing apoptosis and arresting cell-cycle progression; it also has a costimulatory receptor distinct from PD-1 that drives IL-10 and IFN-γ production. Receptor binding studies, T-cell functional assays, apoptosis assays Journal of molecular medicine Medium 12721664
2014 PTEN loss increases PD-L1 cell-surface expression and mRNA levels in breast cancer cells via PI3K/AKT signaling; AKT inhibitor MK-2206 or rapamycin reduces PD-L1 expression; increased PD-L1 from PTEN loss leads to decreased T-cell proliferation and increased T-cell apoptosis in co-culture. PTEN shRNA knockdown in stable cell lines, flow cytometry, Western blot, PI3K pathway inhibitor treatment (MK-2206, rapamycin), T-cell co-culture assays Cancer immunology research High 24764583
2016 MYC oncogene directly binds the promoter of the Pd-l1 (Cd274) gene to transcriptionally activate PD-L1 expression; MYC inactivation in mouse tumors downregulates PD-L1 and enhances antitumor immune response; forced PD-L1 expression during MYC inactivation suppresses immune response and tumor regression. ChIP (MYC binding to Cd274 promoter), genetic MYC inactivation in mouse tumor models, enforced PD-L1 expression rescue experiments, mRNA/protein measurements Science High 26966191
2016 CSN5 (COP9 signalosome 5), induced by NF-κB p65 downstream of TNF-α signaling, deubiquitinates and stabilizes PD-L1, preventing its proteasomal degradation; curcumin inhibits CSN5 and reduces PD-L1 expression. Co-immunoprecipitation, ubiquitination assays, NF-κB inhibition, CSN5 knockdown/overexpression, Western blot, pharmacological inhibition with curcumin Cancer cell High 27866850
2017 CMTM6 (and its closest family member CMTM4, but not other CMTM members) associates with PD-L1 protein at the cell surface, reduces PD-L1 ubiquitination, and increases PD-L1 protein half-life without affecting CD274 transcription, thereby enhancing PD-L1-mediated T-cell inhibition. Haploid genetic screen, haploid genetic modifier screen, genetic complementation, Co-immunoprecipitation, ubiquitination assays, protein half-life measurements, T-cell inhibition assays Nature High 28813410
2005 PD-L1 (CD274) expression in trophoblast cells is regulated by oxygen concentration: low oxygen rapidly downregulates CD274 mRNA (within 4-12 h), and protein levels increase with rising oxygen concentrations, paralleling in vivo expression patterns during placental development. Immunoblot of first- and second-trimester placental lysates, trophoblast cell culture under varying oxygen concentrations, mRNA quantification Biology of reproduction Medium 16251499
2014 Intestinal epithelium-expressed B7-H1 (PD-L1) controls intestinal inflammation independently of adaptive immunity; using bone marrow chimeric and knockout mice, parenchymal (non-hematopoietic) B7-H1 dampens inflammation by inhibiting TNF-α production and stimulating IL-22 secretion from CD11c+CD11b+ lamina propria cells. DSS/TNBS-induced colitis models, B7-H1 knockout mice, bone marrow chimera experiments, cytokine measurement Cell reports High 24529703
2011 B7-H1 (PD-L1) overexpression in keratinocytes accelerates chemically induced squamous cell carcinoma by promoting epithelial-mesenchymal transition (EMT), as evidenced by reduced E-cadherin and elevated Slug/Twist transcription factors in B7-H1 transgenic mouse-derived keratinocytes and SCCs. B7-H1 transgenic mouse model, chemical carcinogenesis model, immunostaining for E-cadherin, Slug, and Twist Cancer research Medium 21730022
2019 Autophagy inhibition increases PD-L1 expression in gastric cancer cells through accumulation of p62/SQSTM1 and consequent NF-κB activation; NF-κB inhibition or p62/SQSTM1 knockdown attenuates PD-L1 upregulation caused by autophagy inhibition. Pharmacological autophagy inhibition, siRNA knockdown, Western blot, flow cytometry, NF-κB inhibition, xenograft experiments Journal of experimental & clinical cancer research Medium 30925913
2017 Tumor-derived exosomes containing noncoding Y RNA hY4 induce PD-L1 expression in monocytes through TLR7 signaling; TLR7-deficient monocytes do not upregulate PD-L1 in response to CLL-derived exosomes or hY4 transfer. RNA sequencing and proteomics of CLL exosomes, transfer of exosomes/hY4 to monocytes, TLR7-knockout monocytes, pharmacological TLR inhibition Science immunology High 28754746
2019 PD-L1 signaling through its intracellular domain delivers pro-survival and stress-resistance signals to cancer cells, functioning as an oncogenic signalosome independent of its immunosuppressive role as a PD-1 ligand. Review/mechanistic synthesis citing functional mutagenesis and downstream signaling pathway studies Signal transduction and targeted therapy Low 30275987
2019 Nonclassical monocytes (NCMs) constitutively express PD-L1 and use this PD-L1 to exert immunomodulatory function by promoting T-cell apoptosis within tertiary lymphoid organs; conversion of classical monocytes to NCMs requires contact with endosteal vessels. Two-photon microscopy, flow cytometry, bone marrow vasculature imaging, PD-L1+ NCM functional T-cell apoptosis assays in TLOs Science immunology Medium 31227596
2022 PD-L1 is phosphorylated by casein kinase 2 (CK2) at Thr285 and Thr290, disrupting PD-L1 binding to SPOP (adaptor of CUL3 ubiquitin E3 ligase), thereby protecting PD-L1 from CUL3-mediated proteasomal degradation and stabilizing it; CK2 inhibition decreases PD-L1 levels, releases CD80 on dendritic cells, and reactivates T-cell function. In vitro kinase assays, Co-immunoprecipitation, site-directed mutagenesis, ubiquitination assays, CK2 inhibitor treatment, dendritic cell functional assays, syngeneic mouse model Cancer research High 35385574
2022 PD-1/PD-L1 signaling regulates T cell lymphatic transendothelial migration: activated Tregs use PD-1/PD-L1 and activated CD4 Teffs use CD80/PD-L1 to cross lymphatic endothelial cells (LECs); PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate VE-cadherin junctions, and through NFκB-p65 to upregulate VCAM-1 on LECs. Antibody blockade experiments, transendothelial migration assays in vitro and in vivo, signaling pathway inhibitors (PI3K/Akt, ERK, NFκB), VE-cadherin and VCAM-1 functional assays Nature communications High 35449134
2022 Senescent cells upregulate PD-L1 in a manner dependent on the proinflammatory SASP program and JAK-STAT signaling; secreted factors from senescent cells are sufficient to upregulate PD-L1 in non-senescent cells via JAK-STAT; rapamycin downregulates PD-L1 in senescent cells. Senescence induction, conditioned media transfer, JAK-STAT inhibition, rapamycin treatment, Western blot, aged mouse tissue analysis Molecular and cellular biology Medium 36154662
2023 SGLT2 co-localizes with PD-L1 at the plasma membrane and recycling endosomes, preventing PD-L1 proteasome-mediated degradation; canagliflozin disrupts SGLT2-PD-L1 interaction, allowing recognition by Cullin3-SPOP E3 ligase leading to PD-L1 ubiquitination and proteasomal degradation. Co-localization imaging, Co-immunoprecipitation, ubiquitination assays, SGLT2 silencing, canagliflozin treatment, syngeneic and humanized mouse models Journal of clinical investigation High 36594471
2020 eEF2K (an atypical protein kinase) promotes translation of PD-L1 mRNA by attenuating the inhibitory effect of an upstream open reading frame (uORF) with a non-canonical CUG start codon in the PD-L1 5'-UTR; eEF2K ablation reduces PD-L1 protein levels and increases cancer cell vulnerability to NK cell killing. eEF2K knockdown/knockout, polyribosome profiling, uORF reporter assays, NK cell cytotoxicity assays Biochemical journal High 33094805
2024 PD-L1 directly interacts with MAP1LC3B (LC3) and localizes to phagosomes; baicalein potentiates the CD274-LC3 interaction to facilitate autophagic-lysosomal degradation of PD-L1, boosting T-cell-mediated antitumor immunity. Co-immunoprecipitation, bimolecular fluorescence complementation (BiFC), microscale thermophoresis, surface plasmon resonance, autophagy flux assays, mouse tumor models Autophagy Medium 39710370
2024 PD-L1 specifically enriches in phagosomes containing yeast (but not bacteria) and directly binds to yeast; the fungal ribosomal protein Rpl20b was identified as a PD-L1 ligand; PD-L1-dependent detection of Rpl20b cross-regulates IL-10 production induced by other innate immune receptors. Proximity labeling of phagosomal contents (PhagoPL), surface display library screening to identify fungal ligand, auxin-inducible PD-L1 depletion system, cytokine measurement Nature High 38839956
2024 TRAF6 stabilizes YAP1 through K63-linked poly-ubiquitination, promoting formation of a YAP1/TFCP2 transcriptional complex that drives PD-L1 transcription in melanoma; TRAF6 suppression reduces membrane PD-L1 and enhances CD8+ T-cell cytolytic activity. CRISPR interference screening, Co-immunoprecipitation, K63-ubiquitination assays, transcription factor binding assays, in vitro and in vivo tumor models, flow cytometry Cancer letters Medium 38583649
2018 PD-L1 constitutively expressed on corneal epithelial cells negatively regulates innate immune clearance of HSV-1: B7-H1-deficient mice show increased chemokine expression, enhanced monocyte/macrophage infiltration, and decreased corneal HSV-1 titers; bone marrow chimera experiments demonstrate the effect is from non-hematopoietic (corneal) PD-L1. B7-H1 knockout mice, local antibody blockade, bone marrow chimera experiments, viral titer measurement, flow cytometry Journal of immunology High 29669784

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature medicine 4084 12091876
1999 B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature medicine 2057 10581077
2016 PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Science translational medicine 2016 26936508
2018 Regulation and Function of the PD-L1 Checkpoint. Immunity 1759 29562194
2016 MYC regulates the antitumor immune response through CD47 and PD-L1. Science (New York, N.Y.) 1156 26966191
2014 PD-L1 expression in triple-negative breast cancer. Cancer immunology research 1123 24764583
2019 Mechanisms Controlling PD-L1 Expression in Cancer. Molecular cell 845 31668929
2016 Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer cell 677 27866850
2017 Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 575 28813410
2019 Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. Journal of hematology & oncology 563 31488176
2016 PD-L1 Expression in Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 377 27117833
2020 Regulation of PD-L1 Expression by NF-κB in Cancer. Frontiers in immunology 309 33324403
2016 What does PD-L1 positive or negative mean? The Journal of experimental medicine 272 27903604
2017 PD-L1. Journal of clinical pathology 263 29097600
2020 PD-L1 degradation pathway and immunotherapy for cancer. Cell death & disease 253 33159034
2017 Tumor-derived exosomes modulate PD-L1 expression in monocytes. Science immunology 251 28754746
2018 The intracellular signalosome of PD-L1 in cancer cells. Signal transduction and targeted therapy 246 30275987
2003 B7-H1 pathway and its role in the evasion of tumor immunity. Journal of molecular medicine (Berlin, Germany) 228 12721664
2015 PD-L1 expression in small cell neuroendocrine carcinomas. European journal of cancer (Oxford, England : 1990) 215 25582496
2016 Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut 191 27196573
2009 B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood 187 19597183
2019 Autophagy inhibition enhances PD-L1 expression in gastric cancer. Journal of experimental & clinical cancer research : CR 146 30925913
2017 Comprehensive screening for PD-L1 expression in thyroid cancer. Endocrine-related cancer 142 28093480
2017 PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma. Oncotarget 142 28445951
2014 Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation. Cancer journal (Sudbury, Mass.) 141 25098285
2015 Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma. Oncotarget 135 25609200
2011 The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T lymphocyte exhaustion. Journal of biomedicine & biotechnology 116 21960736
2017 Imaging PD-L1 Expression with ImmunoPET. Bioconjugate chemistry 101 29125731
2014 PD1 (CD279) and PD-L1 (CD274, B7H1) expression in primary central nervous system lymphomas (PCNSL). Clinical neuropathology 101 24359606
2017 Functional Expression of Programmed Death-Ligand 1 (B7-H1) by Immune Cells and Tumor Cells. Frontiers in immunology 100 28848559
2022 Upregulation of PD-L1 in Senescence and Aging. Molecular and cellular biology 97 36154662
2016 Genomic Amplification of CD274 (PD-L1) in Small-Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 97 27620277
2017 PD-1, PD-L1 (B7-H1) and Tumor-Site Immune Modulation Therapy: The Historical Perspective. Journal of hematology & oncology 95 28122590
2017 Comprehensive analysis of PD-L1 expression in glioblastoma multiforme. Oncotarget 84 28178682
2016 Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 83 27813511
2015 PD-L1 blockade for cancer treatment: MEDI4736. Seminars in oncology 83 25965366
2019 Base excision repair regulates PD-L1 expression in cancer cells. Oncogene 82 30755733
2018 [Predictive value of PD-L1 diagnostics]. Der Pathologe 82 30367225
2023 PD-L1 testing by immunohistochemistry in immuno-oncology. Biomolecules & biomedicine 80 35964287
2020 IRE1α regulates macrophage polarization, PD-L1 expression, and tumor survival. PLoS biology 76 32520957
2023 Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling. The Journal of clinical investigation 74 36594471
2017 Clinical applications of PD-L1 bioassays for cancer immunotherapy. Journal of hematology & oncology 74 28514966
2024 PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders. Molecular therapy : the journal of the American Society of Gene Therapy 72 39342430
2016 PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients. Oncoimmunology 72 28197377
2017 PD-L1 expression in extrahepatic cholangiocarcinoma. Histopathology 68 28419539
2023 PD-L1: expression regulation. Blood science (Baltimore, Md.) 67 37228770
2022 PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration. Nature communications 64 35449134
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
2021 Optimized PD-L1 scoring of gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 62 33954872
2019 Beyond PD-L1 Markers for Lung Cancer Immunotherapy. International journal of molecular sciences 57 31003463
2015 TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer letters 57 25697485
2014 Tissue-expressed B7-H1 critically controls intestinal inflammation. Cell reports 57 24529703
2005 Trophoblast CD274 (B7-H1) is differentially expressed across gestation: influence of oxygen concentration. Biology of reproduction 55 16251499
2018 Gene code CD274/PD-L1: from molecular basis toward cancer immunotherapy. Therapeutic advances in medical oncology 53 30574211
2014 PD-1 and PD-L1 antibodies for melanoma. Human vaccines & immunotherapeutics 53 25625924
2019 PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Science immunology 52 31227596
2018 PD-L1 expression in medulloblastoma: an evaluation by subgroup. Oncotarget 50 29721192
2017 Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential. Autophagy 50 28368722
2018 Efficient PD-L1 gene silence promoted by hyaluronidase for cancer immunotherapy. Journal of controlled release : official journal of the Controlled Release Society 49 30476528
2020 Cytology for PD-L1 testing: A systematic review. Lung cancer (Amsterdam, Netherlands) 48 32007657
2022 Phosphorylation and Stabilization of PD-L1 by CK2 Suppresses Dendritic Cell Function. Cancer research 47 35385574
2021 The role of exosomal PD-L1 in tumor immunotherapy. Translational oncology 47 33647542
2017 Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma. Human pathology 47 28811252
2016 PD-L1 Status in Refractory Lymphomas. PloS one 47 27861596
2021 PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends in molecular medicine 46 34187739
2019 The expression of PD-L1 in salivary gland carcinomas. Scientific reports 45 31484986
2021 Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy. Journal of immunology research 44 33628854
2018 Analysis of PD-L1 expression in trophoblastic tissues and tumors. Human pathology 44 30339966
2021 Non-cytomembrane PD-L1: An atypical target for cancer. Pharmacological research 39 34174446
2021 Emerging role of PD-L1 modification in cancer immunotherapy. American journal of cancer research 39 34522452
2018 PD-L1 expression in malignant salivary gland tumors. BMC cancer 39 29409471
2018 Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors. Endocrine-related cancer 38 29326364
2017 Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor. Cancer medicine 38 28925087
2015 PD-L1 inhibition with MPDL3280A for solid tumors. Seminars in oncology 38 25965367
2011 Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis. Cancer research 37 21730022
2020 eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA. The Biochemical journal 36 33094805
2019 Glial Cell Expression of PD-L1. International journal of molecular sciences 36 30987269
2022 Exosomal PD-L1 predicts response with immunotherapy in NSCLC patients. Clinical and experimental immunology 35 35514075
2017 PD-L1 inhibitors in the pipeline: Promise and progress. Oncoimmunology 34 29296516
2020 Immune Escape Mediated by Exosomal PD-L1 in Cancer. Advanced biosystems 33 32383351
2017 CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients. Histopathology 33 28795418
2024 Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor. Nature 31 38839956
2020 Protein homodimer sequestration with small molecules: Focus on PD-L1. Biochemical pharmacology 29 31972166
2019 Recurrent PDL1 expression and PDL1 (CD274) copy number alterations in breast implant-associated anaplastic large cell lymphomas. Human pathology 29 31125630
2017 New Dancing Couple: PD-L1 and MicroRNA. Scandinavian journal of immunology 29 28675453
2021 Expression of PD-L1 in EBV-associated malignancies. International immunopharmacology 28 33765613
2010 B7-H1 expression in vestibular schwannomas. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 28 20601920
2003 Immunology of B7-H1 and its roles in human diseases. International journal of hematology 28 14686489
2023 Regulation of PD-L1 Trafficking from Synthesis to Degradation. Cancer immunology research 27 37290119
2019 PD-L1 expression in gastroesophageal dysplastic lesions. Virchows Archiv : an international journal of pathology 27 31724072
2024 TRAF6 enhances PD-L1 expression through YAP1-TFCP2 signaling in melanoma. Cancer letters 25 38583649
2024 Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity. Autophagy 25 39710370
2018 PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas. Journal of immunology (Baltimore, Md. : 1950) 25 29669784
2025 PD-L1 as a Biomarker in Gastric Cancer Immunotherapy. Journal of gastric cancer 24 39822174
2018 PD-L1 expression in meningiomas. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 23 30153998
2020 How microRNAs affect the PD-L1 and its synthetic pathway in cancer. International immunopharmacology 22 32416456
2019 Nuclear localization of PD-L1: artifact or reality? Cellular oncology (Dordrecht, Netherlands) 22 30680705
2018 PD-L1 expression in inflammatory myofibroblastic tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 22 29449680
2016 PD-L1 in melanoma: facts and myths. Melanoma management 22 30190888

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