Affinage

PDCD1

Programmed cell death protein 1 · UniProt Q15116

Length
288 aa
Mass
31.6 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDCD1 (PD-1) is an inducible inhibitory immune receptor that, upon engagement by its ligands PD-L1 and PD-L2, restrains antigen-receptor signaling to enforce peripheral tolerance and limit antiretumor and antimicrobial immunity (PMID:18173375, PMID:25098287). Mechanistically, ligand-bound PD-1 recruits the tyrosine phosphatase SHP-2 to dephosphorylate membrane-proximal TCR signaling components, thereby inhibiting T cell proliferation, cytokine production, and cytolytic function in a manner distinct from CTLA-4 (PMID:17606980, PMID:25098287); biophysically, this disrupts the cooperative TCR-pMHC-CD8 trimolecular interaction, reducing T cell spreading and bond lifetimes in an SHP- and Lck-dependent fashion (PMID:33980853). PD-1 surface expression and signaling output are tightly tuned: transcription is driven by NFAT in CD4 T cells and by NF-κB in macrophages (PMID:25810391); N-glycosylation, particularly at N58, controls protein stability, surface localization, and PD-L1 binding (PMID:32156778, PMID:33063473); and surface abundance is set by competing ubiquitination via the KLHL22/Cul3 E3 ligase that degrades PD-1 before surface transport and deubiquitination/stabilization by USP5 downstream of ERK-mediated Thr234 phosphorylation (PMID:37208329, PMID:33109719). PD-1 also forms transmembrane-domain-mediated dimers whose dimerization propensity correlates with inhibitory potency (PMID:38457513), and its exon 3 alternative splicing is governed by MATR3 acting through the ESE3b enhancer (PMID:31441370). Physiologically, PD-1 supports peripheral induced Treg differentiation and CD8 T cell tolerance in tissues such as skin (PMID:24975127, PMID:37344588), and shapes the TCF1-dependent stem-like CD8 T cell subset that responds to PD-1 blockade during chronic infection (PMID:27501248). Inherited complete PD-1 deficiency in humans causes multilineage lymphocyte dysfunction, susceptibility to tuberculosis, and STAT3-cytokine-driven lymphoproliferative autoimmunity, establishing its non-redundant tolerogenic role (PMID:34183838). Beyond T cells, PD-1 is expressed on tumor-associated macrophages where it suppresses phagocytosis, glycolysis, and antigen presentation through mTORC1-dependent feedback (PMID:28514441, PMID:38867043), and on aged podocytes where it drives senescence-associated phenotypes (PMID:35968783).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2007 High

    Established the proximal biochemical mechanism of PD-1 inhibition by showing ligand engagement recruits the phosphatase SHP-2 to antigen-receptor signaling machinery.

    Evidence Biochemical phosphatase recruitment assays following PD-L1/PD-L2 engagement

    PMID:17606980

    Open questions at the time
    • Did not resolve which TCR substrates are dephosphorylated
    • SHP-1 versus SHP-2 contributions not delineated here
  2. 2008 High

    Defined the receptor-ligand topology of the pathway, identifying PD-L1 and PD-L2 as PD-1 ligands and an additional inhibitory PD-L1/B7-1 axis regulating tolerance.

    Evidence Binding partner identification and functional immunological assays in T cells and mouse models

    PMID:18173375

    Open questions at the time
    • Relative in vivo contribution of each ligand interaction not quantified
    • Does not address cell-type-specific ligand usage
  3. 2014 Medium

    Distinguished PD-1 from CTLA-4 mechanistically by localizing PD-1 inhibition to membrane-proximal TCR events, and defined PD-1 as required for peripheral but not thymic Treg differentiation.

    Evidence Primary T cell signaling assays and PD-1-deficient mouse Treg differentiation/suppression assays

    PMID:24975127 PMID:25098287

    Open questions at the time
    • Signaling comparison drawn from review-level synthesis
    • Molecular link between PD-1 signaling and pTreg fate not defined
  4. 2015 High

    Resolved cell-type-specific transcriptional control of PDCD1, showing NF-κB drives macrophage expression while NFAT drives T cell induction.

    Evidence Promoter mutagenesis, ChIP for NF-κB p65, and cyclosporin A dissection in primary macrophages and T cells

    PMID:25810391

    Open questions at the time
    • Full set of regulatory elements not mapped
    • Does not address chromatin state or enhancer dynamics during exhaustion
  5. 2016 High

    Identified the cellular target of PD-1 blockade as a TCF1-dependent stem-like CD8 T cell subset that self-renews and seeds terminally exhausted cells.

    Evidence Chronic LCMV mouse model, PD-1 blockade, transcriptomics, TCF1-deficient mice, and cell fate tracking

    PMID:27501248

    Open questions at the time
    • Direct molecular signaling from PD-1 to TCF1 program not established
    • Human correlate not tested in this study
  6. 2017 High

    Extended PD-1 function beyond T cells by demonstrating macrophage PD-1 restrains tumor-cell phagocytosis, with blockade acting in a macrophage-dependent manner.

    Evidence Flow cytometry of mouse/human TAMs, in vivo PD-1/PD-L1 blockade, and macrophage depletion

    PMID:28514441

    Open questions at the time
    • Signaling pathway downstream of macrophage PD-1 not defined in this study
    • Does not separate direct macrophage effect from T cell crosstalk fully
  7. 2019 High

    Uncovered post-transcriptional control of PD-1 by defining MATR3 as a splicing activator for PDCD1 exon 3 acting through the ESE3b enhancer, counteracted by RNA structure and DDX5.

    Evidence Minigene splicing assays, RNA-affinity chromatography, mass spectrometry, and MATR3 depletion/overexpression

    PMID:31441370

    Open questions at the time
    • Functional consequence of the PD-1Δ3 isoform in vivo not established
    • Physiological signals that tune splicing not identified
  8. 2020 High

    Established that N-glycosylation controls PD-1 stability, surface localization, and ligand/antibody binding, with N58 critical for PD-L1 and camrelizumab engagement.

    Evidence Glycosylation-site mutagenesis, binding assays, surface localization studies, and a camrelizumab/PD-1 crystal structure

    PMID:32156778 PMID:33063473

    Open questions at the time
    • Enzymes generating specific glycoforms not identified
    • Link between TCR-induced glycoform changes and inhibitory output not quantified
  9. 2020 High

    Defined a degradative arm of PD-1 surface control, showing the KLHL22/Cul3 E3 ligase ubiquitinates PD-1 before surface transport to limit its accumulation.

    Evidence Co-IP, ubiquitination assays, KLHL22 knockout/knockdown, surface PD-1 flow cytometry, and tumor models

    PMID:33109719

    Open questions at the time
    • Subcellular site of ubiquitination not precisely localized
    • Signals regulating KLHL22 activity unknown
  10. 2021 High

    Provided biophysical mechanism showing PD-1 disrupts cooperative TCR-pMHC-CD8 trimolecular antigen recognition in an SHP- and Lck-dependent manner.

    Evidence Biophysical force measurements, quantitative imaging of T cell-pMHC interactions, and SHP/Lck perturbation

    PMID:33980853

    Open questions at the time
    • Direct phosphatase substrate at the CD8 coreceptor not identified
    • In vivo relevance of altered bond lifetimes not measured
  11. 2021 High

    Demonstrated the non-redundant human role of PD-1 through an inherited complete deficiency causing multilineage lymphocyte loss, tuberculosis susceptibility, and STAT3-cytokine-driven autoimmunity.

    Evidence Human genetics of PDCD1 loss-of-function with immunophenotyping, functional T cell and cytokine assays

    PMID:34183838

    Open questions at the time
    • Single-patient inborn error limits generalization
    • Mechanistic basis for selective lineage depletion not fully resolved
  12. 2022 Medium

    Connected PD-1 to senescence biology, showing PD-L1+ senescent cells evade CD8 surveillance and PD-1 blockade clears senescent cells, while PD-1 in podocytes drives senescence-associated phenotypes during aging.

    Evidence Single-cell p16 analysis with CD8 depletion epistasis; in vitro podocyte signaling plus anti-PD-1 treatment in aged/FSGS mouse models

    PMID:35968783 PMID:36323784

    Open questions at the time
    • Podocyte-intrinsic PD-1 signaling pathway not fully defined
    • Whether senescent-cell clearance is purely T cell-extrinsic to podocyte PD-1 unresolved
  13. 2023 High

    Showed PD-1 enforces tissue tolerance by preventing antigen-specific effector CD8 T cells from acquiring a fully pathogenic state in skin, with human irAE relevance.

    Evidence Skin-antigen mouse model with PD-1 KO, transcriptomics, CD8 functional assays, and human lichenoid irAE biopsy transcriptomics

    PMID:37344588

    Open questions at the time
    • Molecular checkpoint within the differentiation trajectory not pinpointed
    • Generalizability to non-skin tissues not tested
  14. 2023 High

    Identified a stabilizing arm of PD-1 abundance control, showing ERK-mediated Thr234 phosphorylation recruits USP5 to deubiquitinate and stabilize PD-1.

    Evidence Reciprocal Co-IP, ubiquitination assays, Thr234 mutagenesis, and T cell-specific Usp5 knockout tumor models

    PMID:37208329

    Open questions at the time
    • Interplay between USP5 stabilization and KLHL22 degradation not integrated
    • Upstream triggers of ERK-Thr234 phosphorylation not defined
  15. 2024 High

    Defined PD-1 dimerization and macrophage metabolic feedback as determinants of inhibitory potency, linking transmembrane-domain dimerization to function and mTORC1/glycolysis to macrophage PD-1 induction.

    Evidence Transmembrane-domain mutagenesis with functional T cell/tumor/autoimmunity assays; macrophage stimulation, mTORC1 inhibition, and myeloid-specific PD-1 KO with glycolysis/antigen-presentation readouts

    PMID:38457513 PMID:38867043

    Open questions at the time
    • Structural basis of dimer assembly not solved
    • How dimerization mechanistically amplifies SHP recruitment not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing ubiquitination/deubiquitination, glycosylation, dimerization, and splicing inputs are integrated to set PD-1 inhibitory output in a given cell type remains unresolved.
  • No unified model linking surface-abundance control to signaling strength
  • Non-T-cell PD-1 signaling cascades (macrophage, podocyte) incompletely mapped
  • Direct phosphatase substrate set not fully enumerated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3
Partners
CD274KLHL22MATR3PDCD1LG2PTPN11USP5

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 PD-1 delivers inhibitory signals by interacting with its ligands PD-L1 and PD-L2; additionally, B7-1 was identified as a binding partner for PD-L1, revealing an inhibitory bidirectional interaction between PD-L1 and B7-1 that regulates T cell activation and tolerance. Binding partner identification; functional immunological assays in T cells and mouse models Annual review of immunology High 18173375
2007 PD-1 negatively regulates antigen receptor signaling by recruiting the protein tyrosine phosphatase SHP-2 upon interacting with either PD-L1 or PD-L2. Biochemical signaling assays; phosphatase recruitment studies International immunology High 17606980
2017 Tumour-associated macrophages (TAMs) express PD-1, and PD-1 expression on TAMs correlates negatively with phagocytic potency against tumour cells. Blockade of PD-1/PD-L1 in vivo increases macrophage phagocytosis, reduces tumour growth, and lengthens survival in mouse cancer models in a macrophage-dependent fashion. Flow cytometry of mouse and human TAMs; in vivo PD-1/PD-L1 blockade in mouse cancer models; macrophage depletion experiments Nature High 28514441
2020 PD-1 is extensively N-glycosylated in T cells; glycosylation is critical for PD-1 protein stability and cell surface localization. Glycosylation at the N58 site is essential for mediating PD-1 interaction with PD-L1. TCR activation alters the intensities of specific PD-1 glycoforms. Glycosylation assays; mutagenesis of N-glycosylation sites (N58 and others); cell surface localization studies; PD-L1 binding assays with glycosylation-deficient PD-1 Cancer research High 32156778 33063473
2020 N-glycosylation of asparagine 58 (N58) of PD-1 promotes the interaction with the anti-PD-1 antibody camrelizumab. Crystal structure of the camrelizumab/PD-1 complex shows camrelizumab primarily uses its heavy chain to bind PD-1 while the light chain sterically inhibits PD-L1 binding. Non-glycosylated PD-1 shows substantially decreased binding affinity for camrelizumab. Crystal structure of camrelizumab/PD-1 complex; binding affinity assays with glycosylated vs. non-glycosylated PD-1; N-glycan composition analysis EMBO reports High 33063473
2021 PD-1 signaling suppresses TCR-CD8 cooperativity during T cell antigen recognition: PD-1/PD-L1 engagement results in smaller T cell spreading area, fewer molecular bonds formed, and shorter bond lifetimes of T cell interaction with peptide-MHC, in a manner dependent on SHP phosphatases and Leukocyte C-terminal Src kinase (Lck). PD-1 disrupts the cooperative TCR-pMHC-CD8 trimolecular interaction and prevents CD8 from augmenting antigen recognition. Biophysical force measurements; quantitative imaging of T cell-pMHC interactions; SHP inhibition and Lck perturbation experiments Nature communications High 33980853
2024 PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions. Propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor immunity, cytotoxic T cell function, and autoimmune tissue destruction. Biochemical dimerization assays; transmembrane domain mutational analysis; functional T cell assays; in vivo mouse models of antitumor immunity and autoimmunity Science immunology High 38457513
2023 USP5 is a deubiquitinase for PD-1 that interacts with PD-1 and promotes its deubiquitination and stabilization. ERK phosphorylates PD-1 at Thr234, which promotes PD-1 interaction with USP5. Conditional T cell-specific knockout of Usp5 increases effector cytokine production and retards tumor growth in mice. Co-immunoprecipitation; ubiquitination assays; phosphorylation site mutagenesis (Thr234); conditional Usp5 knockout mice; in vivo tumor models Nature communications High 37208329
2020 KLHL22, an adaptor of the Cul3-based E3 ubiquitin ligase, is a major PD-1-associated protein that mediates ubiquitination and degradation of PD-1 before its transport to the cell surface. KLHL22 deficiency leads to overaccumulation of PD-1, suppressing antitumor T cell responses. Co-immunoprecipitation; ubiquitination assays; KLHL22 knockout/knockdown; flow cytometry of surface PD-1; in vivo tumor models Proceedings of the National Academy of Sciences of the United States of America High 33109719
2015 NF-κB regulates PD-1 expression in macrophages. An NF-κB binding site located upstream of the PDCD1 gene in conserved region C is required for NF-κB-dependent PD-1 gene activation in macrophages stimulated with LPS. Chromatin immunoprecipitation showed NF-κB p65 binding to this region. In CD4 T cells, PD-1 induction requires NFAT (blocked by cyclosporin A); in macrophages, LPS-induced PD-1 expression is cyclosporin A-insensitive. NF-κB binding site deletion/mutagenesis; chromatin immunoprecipitation (ChIP); cyclosporin A pharmacological inhibition; stimulation of primary macrophages and T cells Journal of immunology High 25810391
2014 PD-1 engagement by its ligands inhibits T cell proliferation, cytokine production, and cytolytic function by inhibiting membrane-proximal T cell signaling events, in a mechanism distinct from CTLA-4 (which targets more downstream signaling pathways). PD-1 ligation inhibits TCR proximal signaling via phosphatase recruitment. Primary T cell signaling assays; pharmacological inhibition; comparison with CTLA-4 signaling Cancer journal Medium 25098287
2014 PD-1 is dispensable for thymic T regulatory (Treg) cell development and suppressive function, but is critical for extrathymic differentiation of peripherally induced Treg (pTreg) cells in vivo. In PD-1-deficient mice, conventional CD4+ T cells showed markedly diminished differentiation into pTreg cells across three different in vivo experimental settings. PD-1-deficient mice; in vivo and in vitro Treg differentiation assays; suppression assays with PD-1−/− Tregs European journal of immunology High 24975127
2021 In a patient with inherited complete PD-1 deficiency, leukocytes did not express PD-1 or respond to PD-1-mediated suppression. The patient had depletion of Vδ2+ γδ T, mucosal-associated invariant T (MAIT), and CD56bright NK lymphocytes, with other T cell dysfunction resulting in reduced IFN-γ production upon mycobacterial stimuli and susceptibility to tuberculosis. Expansion of RORγT+ CD4-CD8- double-negative αβ T cells driven by excessive STAT3-activating cytokines (IL-6, IL-23) led to lymphoproliferative autoimmunity. Human genetics (inherited PDCD1 loss-of-function); immunophenotyping; functional T cell assays; cytokine measurement; transcription factor analysis Nature medicine High 34183838
2019 MATR3 is a splicing activator for PDCD1 exon 3 splicing, operating through binding to the ESE3b splicing enhancer in exon 3. MATR3's splicing-stimulatory activity is counteracted by an RNA secondary structure around ESE3b and an RNA helicase DDX5. Two splicing enhancers (ESE3a and ESE3b) in exon 3 regulate alternative splicing of PDCD1 to generate the exon 3-skipped isoform PD-1Δ3. Minigene splicing assays; deletion analysis; mutagenesis; RNA-affinity chromatography; mass spectrometry; MATR3 depletion and overexpression RNA biology High 31441370
2024 In obesity, type I inflammatory cytokines and obesity-linked molecules (IFN-γ, TNF, leptin, insulin, palmitate) induce macrophage PD-1 expression in an mTORC1- and glycolysis-dependent manner. PD-1 then provides negative feedback to TAMs, suppressing glycolysis, phagocytosis, and T cell stimulatory potential. Myeloid-specific PD-1 deficiency slows tumor growth, enhances TAM glycolysis and antigen-presentation, and increases CD8+ T cell activity. In vitro macrophage stimulation assays; mTORC1 inhibition; myeloid-specific PD-1 KO mice; glycolysis measurements; flow cytometry of MHC/CD86 expression and T cell activation Nature High 38867043
2023 PD-1 maintains peripheral CD8 T cell tolerance in skin by preventing tissue-infiltrating antigen-specific effector CD8 T cells from acquiring a fully pathogenic differentiation state, secreting effector molecules, and gaining access to epidermal antigen-expressing cells. In the absence of PD-1, epidermal antigen-expressing cells were eliminated by CD8 T cells, causing local pathology. Mouse model with skin-specific T cell antigen expression; PD-1 KO; transcriptomic analysis; CD8 T cell functional assays; analysis of human skin biopsies from lichenoid irAE patients Nature High 37344588
2022 PD-1 signaling in podocytes contributes to kidney aging: increased PD-1 expression in aged podocytes promotes a senescence-associated secretory phenotype (SASP) and reduces cell survival in vitro. Anti-PD-1 antibody treatment in aged mice improved the aging phenotype in kidney and liver, specifically extending podocyte lifespan in the glomerulus. In vitro podocyte PD-1 signaling assays; anti-PD-1 antibody treatment of aged mice; transcriptomic and immunohistochemistry studies; focal segmental glomerulosclerosis (FSGS) mouse model The Journal of clinical investigation Medium 35968783
2022 PD-L1+ senescent cells are resistant to CD8+ T cell immune surveillance, whereas PD-L1- senescent cells are sensitive. PD-1 antibody administration to naturally ageing or NASH-model mice reduces total p16+ senescent cells and the PD-L1+ senescent cell population in an activated CD8+ T cell-dependent manner. Single-cell analysis of p16+ cells in vivo; PD-1 antibody treatment of aged and disease mouse models; CD8+ T cell depletion experiments; flow cytometry Nature High 36323784
2016 A proliferative CD8+ T cell subset that responds to PD-1 blockade during chronic LCMV infection is characterized by PD-1 expression alongside costimulatory molecules (ICOS, CD28), a TCF1-dependent gene signature related to memory precursors and stem cells, and exclusive residence in lymphoid tissue T cell zones. This subset undergoes self-renewal and differentiates into terminally exhausted CD8+ T cells. TCF1 has a cell-intrinsic and essential role in generating this subset. Mouse chronic LCMV infection model; PD-1 blockade; transcriptomic profiling; TCF1-deficient mice; cell fate tracking; tissue localization studies Nature High 27501248
2014 Pre-existing CD8+ T cells at the invasive tumor margin that express PD-1, in close proximity to PD-L1-expressing cells, predict response to anti-PD-1 therapy. Responding patients showed proliferation of intratumoral CD8+ T cells that directly correlated with radiographic tumor reduction, consistent with PD-1/PD-L1-mediated adaptive immune resistance as the mechanism of suppression. Quantitative immunohistochemistry; quantitative multiplex immunofluorescence; next-generation TCR sequencing; serial tumor biopsies before and during pembrolizumab therapy Nature Medium 25428505

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. The New England journal of medicine 7570 26028255
2014 PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 5468 25428505
2008 PD-1 and its ligands in tolerance and immunity. Annual review of immunology 4373 18173375
2013 Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. The New England journal of medicine 2788 23724846
2016 Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. The New England journal of medicine 2573 27433843
2016 Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell 2522 26997480
2010 The PD-1 pathway in tolerance and autoimmunity. Immunological reviews 1869 20636820
2017 PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 1818 28514441
2016 Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 1703 27501248
2018 Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. The New England journal of medicine 1626 29658848
2016 Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. Cancer discovery 1092 27903500
2007 PD-1 and PD-1 ligands: from discovery to clinical application. International immunology 1028 17606980
2009 PD-1 signaling in primary T cells. Immunological reviews 630 19426218
2024 Regulatory mechanisms of PD-1/PD-L1 in cancers. Molecular cancer 552 38762484
2017 Cancer immunotherapies targeting the PD-1 signaling pathway. Journal of biomedical science 506 28376884
2015 PD-1/PD-L1 inhibitors. Current opinion in pharmacology 454 26047524
2020 Revisiting the PD-1 pathway. Science advances 418 32948597
2019 Application of PD-1 Blockade in Cancer Immunotherapy. Computational and structural biotechnology journal 399 31205619
2022 Blocking PD-L1-PD-1 improves senescence surveillance and ageing phenotypes. Nature 360 36323784
2012 Role of the PD-1 pathway in the immune response. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 358 22900886
2007 PD-1 and its ligands in T-cell immunity. Current opinion in immunology 349 17433872
2020 Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 347 32036071
2015 PD-1 Restrains Radiotherapy-Induced Abscopal Effect. Cancer immunology research 323 25701325
2011 The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Annals of the New York Academy of Sciences 275 21276005
2020 PD-1 Blockade in Anaplastic Thyroid Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 257 32364844
2017 PD-1 and its ligands are important immune checkpoints in cancer. Oncotarget 254 27974689
2020 The Role of PD-1 in Acute and Chronic Infection. Frontiers in immunology 252 32265932
2021 A snapshot of the PD-1/PD-L1 pathway. Journal of Cancer 226 33854633
2016 PD-1/PD-L and autoimmunity: A growing relationship. Cellular immunology 225 27660198
2016 Genetic and Epigenetic Regulation of PD-1 Expression. Journal of immunology (Baltimore, Md. : 1950) 196 26945088
2019 PD-L1/PD-1 Axis in Glioblastoma Multiforme. International journal of molecular sciences 164 31661771
2017 Role of PD-1 in Immunity and Diseases. Current topics in microbiology and immunology 162 28929192
2018 Engineering PD-1-Presenting Platelets for Cancer Immunotherapy. Nano letters 157 30063143
2022 Biomarkers of response to PD-1 pathway blockade. British journal of cancer 154 35228677
2015 Nivolumab: targeting PD-1 to bolster antitumor immunity. Future oncology (London, England) 154 25798726
2021 Emerging concepts in PD-1 checkpoint biology. Seminars in immunology 152 34006473
2014 Biochemical signaling of PD-1 on T cells and its functional implications. Cancer journal (Sudbury, Mass.) 152 25098287
2019 PD-1 Blockade in Advanced Adrenocortical Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 151 31644329
2015 New immunotherapies targeting the PD-1 pathway. Trends in pharmacological sciences 145 26162965
2017 PD-1/PD-L1 Pathway in Breast Cancer. Oncology research and treatment 144 28346916
2015 NF-κB regulates PD-1 expression in macrophages. Journal of immunology (Baltimore, Md. : 1950) 144 25810391
2020 Targeting Glycosylated PD-1 Induces Potent Antitumor Immunity. Cancer research 139 32156778
2024 Obesity induces PD-1 on macrophages to suppress anti-tumour immunity. Nature 129 38867043
2019 PAK4 inhibition improves PD-1 blockade immunotherapy. Nature cancer 127 34368780
2017 PD-1 and cancer: molecular mechanisms and polymorphisms. Immunogenetics 122 28642997
2020 Sintilimab: A Promising Anti-Tumor PD-1 Antibody. Frontiers in oncology 121 33324564
2015 PD-1 Blockers. Cell 120 26317459
2018 Inhibitors of the PD-1 Pathway in Tumor Therapy. Journal of immunology (Baltimore, Md. : 1950) 117 29311378
2018 Combining chemotherapy with PD-1 blockade in NSCLC. Pharmacology & therapeutics 115 29352857
2012 Role of PD-1 in HIV pathogenesis and as target for therapy. Current HIV/AIDS reports 111 22198819
2023 CYP1B1 inhibits ferroptosis and induces anti-PD-1 resistance by degrading ACSL4 in colorectal cancer. Cell death & disease 108 37059712
2017 PD-1 blockade in advanced NSCLC: A focus on pembrolizumab. Cancer treatment reviews 107 29156447
2014 PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer control : journal of the Moffitt Cancer Center 105 24955707
2016 Features of Memory-Like and PD-1(+) Human NK Cell Subsets. Frontiers in immunology 101 27683578
2014 PD1 (CD279) and PD-L1 (CD274, B7H1) expression in primary central nervous system lymphomas (PCNSL). Clinical neuropathology 101 24359606
2021 Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child. Nature medicine 97 34183838
2018 PD-1/PD-L1 in disease. Immunotherapy 97 29260623
2014 PD-1 regulates extrathymic regulatory T-cell differentiation. European journal of immunology 93 24975127
2013 Manipulating the PD-1 pathway to improve immunity. Current opinion in immunology 89 23582509
2005 PD-1/PD-L pathway and autoimmunity. Autoimmunity 85 16227150
2018 PD-1 immunobiology in systemic lupus erythematosus. Journal of autoimmunity 80 30396745
2010 PD-1, gender, and autoimmunity. Autoimmunity reviews 79 20433954
2023 ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy. Nature communications 76 37208329
2019 Inflammatory myopathy associated with PD-1 inhibitors. Journal of autoimmunity 76 30862448
2020 N-glycosylation of PD-1 promotes binding of camrelizumab. EMBO reports 73 33063473
2014 PD-1 as an immune modulatory receptor. Cancer journal (Sudbury, Mass.) 71 25098286
2020 KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression. Proceedings of the National Academy of Sciences of the United States of America 70 33109719
2022 Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease. The Journal of clinical investigation 69 35968783
2016 Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 69 26843495
2021 PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition. Nature communications 67 33980853
2019 Depletion of PD-1-positive cells ameliorates autoimmune disease. Nature biomedical engineering 66 30952980
2016 Basics of PD-1 in self-tolerance, infection, and cancer immunity. International journal of clinical oncology 65 26864303
2015 Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. Drugs of today (Barcelona, Spain : 1998) 63 25685857
2023 PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 62 37344588
2014 Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma. Virchows Archiv : an international journal of pathology 59 25011996
2024 PD-1 regulation in immune homeostasis and immunotherapy. Cancer letters 57 38401888
2014 PD-1 and PD-L1 antibodies for melanoma. Human vaccines & immunotherapeutics 53 25625924
2013 PD-1 coinhibitory signals: the link between pathogenesis and protection. Seminars in immunology 52 23548749
2020 PD-1: Its Discovery, Involvement in Cancer Immunotherapy, and Beyond. Cells 42 32492969
2020 Combination of PD-L1 and PVR determines sensitivity to PD-1 blockade. JCI insight 41 32554931
2015 Anti-PD-1 therapy in melanoma. Seminars in oncology 41 25965365
2022 PD-1/PD-L Axis in Neuroinflammation: New Insights. Frontiers in neurology 39 35756927
2020 PD-1/PD-L1 in cardiovascular disease. Clinica chimica acta; international journal of clinical chemistry 39 32084380
2018 Clinical Development of PD-1 in Advanced Melanoma. Cancer journal (Sudbury, Mass.) 38 29360722
2018 PD-1 /PD-L1 checkpoint in hematological malignancies. Leukemia research 38 29428449
2021 PD-1 signaling pathway in sepsis: Does it have a future? Clinical immunology (Orlando, Fla.) 37 33905818
2021 PD-1 inhibition in advanced myeloproliferative neoplasms. Blood advances 36 34581778
2020 Regulation of PD-1 in T cells for cancer immunotherapy. European journal of pharmacology 35 32497624
2019 The Controversial Role of PD-1 and Its Ligands in Gynecological Malignancies. Frontiers in oncology 35 31681606
2021 Transcriptional and epigenetic regulation of PD-1 expression. Cellular and molecular life sciences : CMLS 34 33738533
2017 PD-1 signaling and inhibition in AML and MDS. Annals of hematology 33 28643044
2024 Transmembrane domain-driven PD-1 dimers mediate T cell inhibition. Science immunology 32 38457513
2020 The PD-1/PD-L pathway in rheumatic diseases. Journal of the Formosan Medical Association = Taiwan yi zhi 31 32334916
2023 Hyperprogression of cutaneous T cell lymphoma after anti-PD-1 treatment. JCI insight 30 36649072
2019 PD-1 Inhibitors in the Advanced Esophageal Cancer. Frontiers in pharmacology 29 31920637
2022 Strategies for developing PD-1 inhibitors and future directions. Biochemical pharmacology 26 35640711
2022 Combination Approaches to Target PD-1 Signaling in Cancer. Frontiers in immunology 26 35911672
2021 DGKA Mediates Resistance to PD-1 Blockade. Cancer immunology research 26 33608256
2019 Modulation of PDCD1 exon 3 splicing. RNA biology 26 31441370
2019 PD-1/PD-L Pathway Potentially Involved in ITP Immunopathogenesis. Thrombosis and haemostasis 25 30808044

Missed literature

Know a paper Affinage missed for PDCD1? Flag it for the maintainers and the community.

No submissions yet.