Affinage

CD47

Leukocyte surface antigen CD47 · UniProt Q08722

Length
323 aa
Mass
35.2 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD47 is a broadly expressed transmembrane glycoprotein that functions as a central immune checkpoint and integrin co-receptor, integrating phagocytic inhibition, cell adhesion, and pro-apoptotic signaling across hematopoietic, neuronal, and vascular compartments. Its extracellular immunoglobulin variable (IgV) domain engages SIRPα on macrophages, dendritic cells, and NK cells, delivering a 'don't eat me' signal that suppresses phagocytosis through SENP8-mediated deneddylation and activation of SHP-1/SHP-2 phosphatases; this inhibitory axis operates ratiometrically against activating receptors such as FcγR and is species-specific (PMID:10856220, PMID:19144521, PMID:36626230, PMID:34433055, PMID:33416832). CD47 simultaneously forms cholesterol-dependent supramolecular complexes with αvβ3 and other β-integrins and heterotrimeric Gi proteins, coupling thrombospondin-1 binding to cAMP reduction, Rac/Cdc42 activation, integrin avidity modulation, and cell migration (PMID:10085089, PMID:11306274, PMID:14966135, PMID:15215311). CD47 surface levels are transcriptionally controlled by MYC, HIF, and TNF–NF-κB pathways and post-translationally stabilized by EGFR–c-Src phosphorylation at Y288, which blocks TRIM21-mediated ubiquitylation and proteasomal degradation; loss or blockade of CD47 enhances autophagic flux, confers radioprotection, and in the developing brain permits microglial engulfment of synapses in an activity-dependent manner (PMID:26966191, PMID:37541303, PMID:22874555, PMID:30308165).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 Medium

    Establishing that CD47 exists as four alternatively spliced isoforms with tissue-specific expression resolved how a single gene could serve distinct functions in brain, bone marrow, and epithelial compartments.

    Evidence PCR, isoform-specific antibodies, and immunohistochemistry on mouse and human tissue panels

    PMID:8586654

    Open questions at the time
    • Functional differences between isoforms remain largely undefined
    • No structural basis for how cytoplasmic tail variants alter signaling
  2. 1999 High

    Demonstrating that CD47 physically couples to heterotrimeric Gi proteins and β3 integrin in a ternary complex, with thrombospondin-derived peptides stimulating GTPγS binding and cAMP reduction, established CD47 as a bona fide Gi-coupled co-receptor.

    Evidence Immunoprecipitation, affinity chromatography, GTPγS binding, cAMP measurement, and pertussis toxin inhibition in platelets and CHO cells

    PMID:10085089

    Open questions at the time
    • Direct structural interface between CD47 multiply-spanning domain and Gαi not resolved
    • Stoichiometry of the CD47–integrin–Gi complex unknown
  3. 1999 Medium

    The finding that anti-CD47 antibodies induce a rapid, Fas/TNF-independent apoptotic pathway in activated T cells revealed a pro-death signaling capacity distinct from its integrin-modulatory function.

    Evidence Anti-CD47 mAb (Ad22), annexin V/PI staining, and signaling-deficient Jurkat variant panel

    PMID:10358145

    Open questions at the time
    • Downstream death effectors not identified
    • Single antibody epitope; generalizability to physiological ligands unclear
    • Not independently replicated in primary T cells at that time
  4. 2000 High

    The discovery that CD47 knockout red blood cells are rapidly cleared by splenic macrophages established CD47 as a 'marker of self' and defined the foundational concept of a phagocytic checkpoint.

    Evidence CD47-knockout mice, in vivo RBC clearance assay, functional phagocytosis measurement

    PMID:10856220

    Open questions at the time
    • Signaling cascade downstream of SIRPα in macrophages not yet mapped
    • Whether the checkpoint extends to nucleated cells was untested
  5. 2000 High

    Mapping the CD47–SIRPα interaction to their N-terminal IgV domains and linking it to macrophage fusion provided the structural basis for the inhibitory checkpoint and revealed a role in multinucleated giant cell formation.

    Evidence GST-CD47 fusion binding, co-immunoprecipitation, antibody blocking, multinucleation assay

    PMID:10964914

    Open questions at the time
    • Atomic-resolution structure of the CD47–SIRPα interface not yet available
    • Signaling events connecting SIRPα engagement to fusion machinery unknown
  6. 2004 Medium

    Showing that CD47 enhances αvβ3 integrin avidity through both cholesterol-independent clustering and cholesterol-dependent raft recruitment, with only the latter enabling Gi signaling, dissected the dual mechanism by which CD47 modulates integrin function.

    Evidence LIBS mAb integrin activation reporter, chemical crosslinking, methyl-β-cyclodextrin raft disruption, detergent-free fractionation

    PMID:14966135

    Open questions at the time
    • Identity of intermediate signaling molecules between CD47 raft recruitment and Gi activation unknown
    • Applicability to non-αvβ3 integrins untested at this resolution
  7. 2004 Medium

    CD47 overexpression in neurons promoted dendritic outgrowth and upregulated synaptic proteins via MAPK activation, establishing a neuronal signaling role beyond the immune checkpoint function.

    Evidence Viral overexpression, siRNA knockdown, MAPK assay, glutamate release and Ca²⁺ imaging in cortical neurons

    PMID:15297459

    Open questions at the time
    • Which MAPK cascade member is directly activated by CD47 is unresolved
    • Relevance to in vivo synaptogenesis not yet shown at this point
  8. 2007 Medium

    Identification of BNIP3 as a CD47-binding proapoptotic effector that is stabilized by CD47 and mediates TSP-1-dependent T cell apoptosis provided a molecular mechanism for CD47-driven inflammation resolution.

    Evidence CD47-KO and TSP-KO mice, co-immunoprecipitation of CD47–BNIP3, inflammation assays

    PMID:17442977

    Open questions at the time
    • Structural basis of the CD47–BNIP3 interaction not defined
    • Whether BNIP3 pathway operates in non-T cells expressing CD47 unknown
  9. 2007 High

    Demonstrating that porcine CD47 fails to trigger human SIRPα phosphorylation, while human CD47 expression on porcine cells rescues them from phagocytosis, established species specificity as a barrier in xenotransplantation.

    Evidence SIRPα phosphorylation assay, soluble CD47-Fc inhibition, transgenic human CD47 on porcine cells with phagocytosis readout

    PMID:17360380

    Open questions at the time
    • Residues determining species specificity not fully mapped
    • In vivo xenograft survival benefit not quantified long-term
  10. 2009 High

    Consolidating evidence that SIRPα recruits SHP-1/SHP-2 through its cytoplasmic ITIMs upon CD47 ligation unified the phagocytic checkpoint, migration, and neuronal-network regulation under one signaling framework.

    Evidence Biochemical binding, phosphorylation studies, functional phagocytosis and migration assays reviewed

    PMID:19144521

    Open questions at the time
    • Relative contributions of SHP-1 vs. SHP-2 in different cell types unresolved
    • Targets dephosphorylated at the phagocytic cup not catalogued
  11. 2012 High

    The observation that CD47 deficiency or blockade activates autophagic flux and confers radioprotection revealed that CD47 tonically suppresses autophagy, linking the checkpoint receptor to stress resistance.

    Evidence CD47-KO mice and cells, electron microscopy of autophagosomes, LC3/BECN1/ATG5/ATG7/p62 quantification, CD47 re-expression rescue

    PMID:22874555

    Open questions at the time
    • Molecular mechanism by which CD47 suppresses autophagy initiation unknown
    • Whether autophagy regulation is SIRPα-dependent or cell-autonomous not distinguished
  12. 2016 High

    ChIP-validated binding of MYC to the CD47 promoter, with enforced CD47 expression rescuing tumor growth after MYC inactivation, established MYC as a direct transcriptional driver of immune evasion through CD47.

    Evidence ChIP, conditional MYC inactivation in mouse tumors, shRNA, flow cytometry, qRT-PCR, enforced CD47 rescue

    PMID:26966191

    Open questions at the time
    • Whether MYC regulation of CD47 operates in non-transformed tissues unknown
    • Epigenetic co-factors at the CD47 promoter not identified
  13. 2017 High

    Identification of a TNF–NF-κB1-responsive constituent enhancer within a breast-cancer-specific CD47 super-enhancer revealed how inflammatory signaling amplifies CD47 transcription in a context-dependent manner.

    Evidence ChIP-seq, CRISPR enhancer deletion, luciferase reporter, TNF-α stimulation with NF-κB inhibition

    PMID:28378740

    Open questions at the time
    • Whether this super-enhancer operates in non-breast cancer contexts untested
    • Transcription factor co-occupancy at the super-enhancer not fully mapped
  14. 2018 High

    Demonstrating that CD47-deficient mice exhibit excessive microglial engulfment of retinogeniculate synapses and fail to activity-dependently spare active inputs established CD47 as a neuronal 'don't eat me' signal that protects synapses during developmental pruning.

    Evidence CD47-KO mice, confocal engulfment imaging, electrophysiology, activity manipulation

    PMID:30308165

    Open questions at the time
    • Whether microglial SIRPα is the cognate receptor in this context was assumed but not directly tested
    • Mechanism of activity-dependent CD47 regulation on individual synapses unknown
  15. 2021 High

    Quantitative reconstitution showing that macrophage phagocytic decisions depend on a ≥10:1 ratio of activating (FcγR) to inhibitory (SIRPα–CD47) signals, with SIRPα engagement suppressing FcγR phosphorylation, provided a biophysical framework for the checkpoint's signal integration logic.

    Evidence Chimeric receptor reconstitution, quantitative ligand density titration, FcγR phosphorylation assay

    PMID:34433055

    Open questions at the time
    • Whether this ratio threshold applies in vivo with native receptor densities untested
    • Contributions of other 'eat me' and 'don't eat me' signals to the ratio not included
  16. 2021 High

    Discovery that NK cells express functional SIRPα that is upregulated by IL-2 and suppressed by CD47 on targets extended the CD47 checkpoint beyond myeloid phagocytes to innate lymphoid cytotoxicity.

    Evidence NK cell SIRPα expression analysis, cytotoxicity assays, SIRPα-KO, antibody blockade

    PMID:33416832

    Open questions at the time
    • Downstream signaling events in NK cells after SIRPα–CD47 engagement not characterized
    • Whether this axis operates on all NK cell subsets unclear
  17. 2023 High

    Identification of EGFR–c-Src-mediated Y288 phosphorylation that blocks TRIM21-mediated K99/K102 polyubiquitylation and proteasomal degradation of CD47 revealed a post-translational stabilization mechanism exploited by tumors.

    Evidence Co-IP, mass spectrometry, Y288F and K99/102R knock-in mutagenesis, ubiquitylation and phagocytosis assays, in vivo brain tumor model

    PMID:37541303

    Open questions at the time
    • Whether TRIM21-dependent CD47 degradation operates in non-EGFR-driven cancers unknown
    • Other kinases that may phosphorylate Y288 not surveyed
  18. 2023 High

    Demonstrating that SHP2 is constitutively neddylated at K358/K364 to maintain autoinhibition, and that SENP8-mediated deneddylation upon SIRPα engagement activates SHP2 at the phagocytic cup, resolved a missing step in CD47–SIRPα downstream signaling.

    Evidence Mass spectrometry neddylation-site mapping, site-directed mutagenesis, SENP8 knockdown, SHP2 activity and phagocytosis assays

    PMID:36626230

    Open questions at the time
    • How SIRPα engagement triggers SENP8 recruitment or activation is unknown
    • Whether SHP1 is similarly regulated by neddylation untested
  19. 2024 High

    Engineering a CD47 variant (Q31P, '47E') that engages SIRPα but evades therapeutic anti-CD47 antibodies demonstrated that the checkpoint can be harnessed to protect adoptively transferred CAR T cells from macrophage clearance.

    Evidence In vivo CAR T cell clearance, CD47 variant engineering, anti-CD47 antibody treatment, multiple tumor models

    PMID:38750365

    Open questions at the time
    • Long-term immunological consequences of 47E-expressing T cells in patients unknown
    • Whether 47E alters thrombospondin-1 binding or Gi signaling untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for how CD47's multiply-spanning transmembrane domain couples to Gi proteins and integrins; the mechanism by which CD47 tonically suppresses autophagy; and how activity-dependent regulation of CD47 at individual synapses is achieved.
  • No high-resolution structure of full-length CD47 in complex with Gi or integrin
  • Cell-autonomous vs. SIRPα-dependent signaling not fully dissected for autophagy regulation
  • Molecular link between neuronal activity and local CD47 surface expression at synapses unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 5
Partners
BNIP3GNAI2ITGB3SENP8SIRPASRCTHBS1TRIM21
Complex memberships
CD47–SIRPαCD47–αvβ3 integrin–Gi

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CD47 functions as a 'marker of self' on red blood cells by binding to the inhibitory receptor SIRPα on macrophages, thereby preventing phagocytic clearance; CD47-deficient red blood cells are rapidly cleared by splenic red pulp macrophages. In vivo mouse model (CD47 knockout), functional phagocytosis assay, receptor binding Science High 10856220
2001 CD47 (IAP) is a receptor for thrombospondin family members and forms a supramolecular complex with specific integrins (beta1, beta2, beta3 families), heterotrimeric G proteins, and cholesterol; thrombospondin-derived VVM motif peptides act as CD47 agonists initiating Gi protein signaling to augment integrin function. Co-immunoprecipitation, functional assays (platelet activation, cell motility, adhesion) Trends in Cell Biology High 10085089 11306274
1999 CD47 functionally couples to heterotrimeric Gi protein: CD47, its beta3 integrin partner, and Gi proteins form a stable detergent-soluble complex; GTP/AlF4 releases Gialpha from the complex and reduces CD47 agonist peptide binding; thrombospondin-derived 4N1K peptide stimulates GTPγS binding and decreases cAMP in a Gi-dependent manner. Immunoprecipitation, affinity chromatography, GTPγS binding assay, cAMP measurement, pertussis toxin inhibition Journal of Biological Chemistry High 10085089
2000 CD47 interacts with SIRPα (MFR/P84/BIT/SHPS-1) via their amino-terminal immunoglobulin variable domains; this interaction mediates macrophage-macrophage adhesion and fusion leading to multinucleated giant cell formation. GST-CD47 fusion protein binding assay, Co-immunoprecipitation, antibody blocking of fusion, functional multinucleation assay Journal of Biological Chemistry High 10964914
2009 SIRPα binds CD47 and recruits tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region; the CD47-SIRPα interaction regulates cell migration and phagocytosis, and is important for immune homeostasis and neuronal network regulation. Biochemical binding assays, phosphorylation studies, functional migration/phagocytosis assays reviewed Trends in Cell Biology High 19144521
2016 MYC transcription factor directly binds the promoters of CD47 and PD-L1 genes, regulating their expression; MYC inactivation reduces CD47 and PD-L1 protein and mRNA levels and enhances antitumor immune responses; enforced CD47 expression rescues tumor growth after MYC inactivation. ChIP (MYC binding to CD47 promoter), conditional MYC inactivation mouse models, shRNA knockdown, flow cytometry, qRT-PCR Science High 26966191
2007 Species incompatibility of CD47 contributes to xenograft rejection: porcine CD47 fails to induce SIRPα tyrosine phosphorylation in human macrophages; soluble human CD47-Fc inhibits phagocytosis of porcine cells; transgenic expression of human CD47 on porcine cells reduces susceptibility to human macrophage phagocytosis. SIRPα phosphorylation assay, soluble CD47-Fc inhibition assay, transgenic CD47 expression with phagocytosis assay PNAS High 17360380
2004 CD47 forced expression in N1E-115 neuroblastoma cells induces neurite and filopodium formation through activation of Rac and Cdc42; SHPS-1-Fc (CD47 ligand) promotes this effect; neurite formation requires beta3 integrin; filopodium formation requires the entire CD47 structure whereas neurite formation requires only the extracellular region. Forced expression, dominant-negative Rac/Cdc42 inhibition, anti-beta3 antibody blocking, morphological quantification Molecular Biology of the Cell High 15215311
1999 Activation of specific epitopes on the Ig variable domain of CD47 rapidly induces apoptosis in T cells via a novel pathway independent of Fas, TNF receptor, CD3, CD4, CD45, p56lck, and classical DNA fragmentation; this CD47-mediated apoptosis is enhanced by CD3 co-ligation and requires T cell preactivation. Anti-CD47 monoclonal antibody (Ad22), flow cytometry (annexin V, PI), morphological analysis, variant Jurkat cell lines deficient in signaling molecules Journal of Immunology Medium 10358145
2007 CD47 interaction with thrombospondin-1/2 mediates T cell apoptosis via induction of BNIP3 (a proapoptotic Bcl-2 family member); CD47 physically interacts with BNIP3 and inhibits its proteasomal degradation, sensitizing activated T cells to CD47-induced apoptosis; CD47- or TSP-deficient mice show prolonged inflammation due to deficient T cell apoptosis. CD47-knockout and TSP-knockout mouse models, inflammation assay, co-immunoprecipitation of CD47-BNIP3, western blotting Journal of Immunology Medium 17442977
2004 CD47 overexpression in cortical neurons enhances dendritic outgrowth and synaptic protein expression (synaptotagmin, syntaxin, synapsin I, SNAP25), increases glutamate release and Ca2+ oscillations; these effects require MAPK activation; CD47 siRNA knockdown reduces MAPK activity and synaptic protein levels. Viral gene transfer for overexpression, siRNA knockdown, MAPK activity assay, glutamate release measurement, Ca2+ imaging, western blotting Journal of Biological Chemistry Medium 15297459
2004 CD47 enhances alphavbeta3 integrin avidity through cholesterol-independent interactions; both CD47 and IgV-GPI (extracellular IgV domain with GPI anchor) increase the population of activatable integrin molecules and promote clustering of alphavbeta3; CD47, but not IgV-GPI, recruits alphavbeta3 to cholesterol-rich raft domains and enables Gi-dependent signaling. LIBS mAb binding (integrin activation reporter), chemical crosslinking, cholesterol depletion (methyl-beta-cyclodextrin), detergent-free raft fractionation Journal of Biological Chemistry Medium 14966135
1995 CD47 exists as four alternatively spliced forms differing only in their intracytoplasmic C-terminal tails; these splice forms are tissue-specifically expressed (form 2 on bone marrow-derived cells and endothelia, form 4 in brain/peripheral nervous system), and are evolutionarily conserved between mouse and human. PCR, isoform-specific polyclonal antibodies, immunohistochemistry, western blotting on tissue panels Journal of Cell Science Medium 8586654
2012 CD47 deficiency or blockade confers radioprotection by activating autophagic flux; irradiated CD47-deficient T cells and endothelial cells show increased autophagosome formation, elevated BECN1, ATG5, ATG7 and reduced SQSTM1/p62; pharmacological or siRNA inhibition of autophagy selectively sensitizes CD47-deficient cells to radiation; re-expression of CD47 reverses autophagic flux and radiation resistance. CD47 KO mice and cells, electron microscopy (autophagosome), LC3 puncta quantification, gene expression (BECN1, ATG5, ATG7, p62), siRNA, pharmacological autophagy inhibition, CD47 re-expression rescue Autophagy High 22874555
2021 SIRPα is expressed in NK cells and functions as an immune checkpoint; NK cell SIRPα is upregulated by IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters NK stimulatory signals (IL-2, CD16, NKG2D); SIRPα deficiency or antibody blockade increases NK cell killing capacity; this axis is highly species-specific. NK cell SIRPα expression analysis, functional cytotoxicity assays, SIRPα KO, antibody blockade, xenogeneic target cell assays Journal of Experimental Medicine High 33416832
2018 CD47 expression in the developing retinogeniculate system correlates with peak pruning periods; CD47-deficient mice exhibit increased microglial engulfment of retinogeniculate inputs and reduced synapse numbers; CD47 is required for neuronal-activity-mediated changes in engulfment—microglia in CD47-KO mice fail to preferentially engulf less active inputs. CD47-KO mice, immunofluorescence, confocal microscopy of synaptic engulfment, electrophysiology, activity manipulation Neuron High 30308165
2023 EGFR activation induces c-Src binding to CD47, leading to c-Src-mediated phosphorylation of CD47 at Y288; this phosphorylation inhibits the interaction between E3 ubiquitin ligase TRIM21 and CD47, blocking TRIM21-mediated K99/102 polyubiquitylation and proteasomal degradation of CD47; knock-in CD47 Y288F reduces CD47 levels and increases macrophage phagocytosis of tumor cells. Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis (Y288F, K99/102R knock-in), ubiquitylation assay, phagocytosis assay, in vivo brain tumor model Advanced Science High 37541303
2023 CD47/SIRPα axis downstream signaling requires deneddylation of SHP2: SHP2 is constitutively neddylated at K358 and K364 maintaining autoinhibition; upon CD47 ligation of SIRPα, SENP8 deneddylates SHP2, enabling dephosphorylation of substrates at the phagocytic cup and inhibiting macrophage phagocytosis. Mass spectrometry (neddylation site mapping), site-directed mutagenesis, SENP8 knockdown, phagocytosis assay, SHP2 activity assay Journal of Clinical Investigation High 36626230
2021 Macrophage phagocytic decisions are regulated by the ratio of activating (FcγR) to inhibitory (SIRPα-CD47) signals over a broad range of absolute molecular densities; at least 10:1 activating:inhibitory ligand ratios are required to promote phagocytosis; SIRPα engagement reduces FcγR phosphorylation through inhibitory phosphatases recruited to CD47-bound SIRPα. Chimeric receptor reconstitution, quantitative ligand density control on model targets, FcγR phosphorylation assay, tumor cell phagocytosis assay Cell Reports High 34433055
2005 CD47 can induce intercellular adhesion and cell aggregation independent of active integrins and SIRPα, requiring Gi signaling (pertussis toxin-sensitive) and Rac GTPase activation; CD47-expressing cells preferentially bind other CD47-expressing cells; this CD47-mediated cell-cell adhesion modulates lymphocyte migration through fibroblast monolayers. Cell aggregation assay, pertussis toxin treatment, Clostridium difficile toxin B (Rho/Rac inhibitor), GTP-Rac pulldown, Jurkat transmigration assay Journal of Cellular Physiology Medium 15880429
2017 TNF-NF-κB1 signaling directly regulates CD47 expression by interacting with a constituent enhancer located within a CD47-associated super-enhancer specific to breast cancer; disruption of CD47 super-enhancers reduces CD47 gene expression. ChIP-seq, CRISPR-mediated enhancer deletion, luciferase reporter assay, TNF-α stimulation with NF-κB inhibition Nature Communications High 28378740
2018 Chemotherapy-induced upregulation of CD47 is mediated by HIF transcription factors; genetic or pharmacological inhibition of HIFs blocks chemotherapy-induced enrichment of CD47+ breast cancer cells; hypoxic conditions also enrich CD47+ cells via HIF-dependent transcriptional induction. qRT-PCR, flow cytometry, HIF genetic knockdown (shRNA), pharmacological HIF inhibition, hypoxia treatment PNAS Medium 29367423
2022 Extracellular vesicles from CD47-overexpressing cells can induce CD47 'cross-dressing' on recipient pig or human cells; cross-dressed CD47 interacts with SIRPα to inhibit phagocytosis; however, unlike autogenous CD47, ligation of cross-dressed CD47 does not transmit cell death signals. Extracellular vesicle transfer assay, SIRPα binding assay, phagocytosis assay, cell death assay after CD47 ligation eLife Medium 36454036
2024 Anti-CD47 antibodies cause rapid macrophage-mediated clearance of adoptively transferred CAR T cells; engineering CD47 variant Q31P (47E) on T cells engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies, protecting T cells from clearance while still enabling macrophage recruitment to tumors. In vivo CAR T cell clearance assay, CD47 variant engineering, anti-CD47 antibody treatment, tumor growth assay Nature High 38750365
2020 Infected cells upregulate CD47 as a host innate immune checkpoint response to pathogen recognition receptor (PRR) stimulation; CD47 upregulation slows phagocytic uptake and downstream APC functions; CD47 blockade or KO enhances immune responses during LCMV and M. tuberculosis infection; proinflammatory cytokines also upregulate CD47 on uninfected dendritic cells. PRR stimulation experiments, CD47-KO mice, antibody blockade, LCMV and M. tuberculosis infection models, flow cytometry mBio Medium 32576678

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Role of CD47 as a marker of self on red blood cells. Science (New York, N.Y.) 1522 10856220
2016 MYC regulates the antitumor immune response through CD47 and PD-L1. Science (New York, N.Y.) 1139 26966191
1997 The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. The EMBO journal 1060 9384571
2001 Integrin-associated protein (CD47) and its ligands. Trends in cell biology 719 11306274
2016 CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature 550 27437576
2020 The CD47-SIRPα Immune Checkpoint. Immunity 536 32433947
2009 Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway. Trends in cell biology 389 19144521
2018 CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development. Neuron 368 30308165
2004 An IAP-IAP complex inhibits apoptosis. The Journal of biological chemistry 322 15218035
2010 Survivin and IAP proteins in cell-death mechanisms. The Biochemical journal 310 20704571
2016 Durable antitumor responses to CD47 blockade require adaptive immune stimulation. Proceedings of the National Academy of Sciences of the United States of America 306 27091975
2017 Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis. Biomaterials 293 28086180
2017 Cancer immunotherapy targeting the CD47/SIRPα axis. European journal of cancer (Oxford, England : 1990) 287 28286286
2013 Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation. Cold Spring Harbor perspectives in biology 265 23378585
2021 Targeting CD47 for cancer immunotherapy. Journal of hematology & oncology 264 34717705
2007 Role for CD47-SIRPalpha signaling in xenograft rejection by macrophages. Proceedings of the National Academy of Sciences of the United States of America 254 17360380
2018 Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple-negative breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 250 29367423
2017 A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. Nature communications 193 28378740
2022 Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nature medicine 192 35027753
1995 In vivo expression of alternatively spliced forms of integrin-associated protein (CD47). Journal of cell science 189 8586654
2000 CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation. The Journal of biological chemistry 184 10964914
2002 Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nature cell biology 181 12021770
2021 The SIRPα-CD47 immune checkpoint in NK cells. The Journal of experimental medicine 158 33416832
2012 The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Experimental oncology 141 23070005
1999 The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi. The Journal of biological chemistry 139 10085089
2022 Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect. Nature cancer 132 36411318
2020 Role of CD47 in Hematological Malignancies. Journal of hematology & oncology 132 32677994
2015 Survivin - The inconvenient IAP. Seminars in cell & developmental biology 129 25591986
2007 Interactions between CD47 and thrombospondin reduce inflammation. Journal of immunology (Baltimore, Md. : 1950) 128 17442977
2022 CD47-SIRPα-targeted therapeutics: status and prospects. Immuno-oncology technology 123 35754851
2019 SNIPERs-Hijacking IAP activity to induce protein degradation. Drug discovery today. Technologies 123 31200857
2000 Understanding IAP function and regulation: a view from Drosophila. Cell death and differentiation 113 11139277
2014 IAP family of cell death and signaling regulators. Methods in enzymology 109 25065885
2022 CD47/SIRPα axis: bridging innate and adaptive immunity. Journal for immunotherapy of cancer 97 35831032
2024 Engineered CD47 protects T cells for enhanced antitumour immunity. Nature 95 38750365
2015 Cellular IAP proteins and LUBAC differentially regulate necrosome-associated RIP1 ubiquitination. Cell death & disease 94 26111062
1999 CD47 signals T cell death. Journal of immunology (Baltimore, Md. : 1950) 92 10358145
2023 The landscape overview of CD47-based immunotherapy for hematological malignancies. Biomarker research 89 36726125
2022 CD47-SIRPα blocking-based immunotherapy: Current and prospective therapeutic strategies. Clinical and translational medicine 87 35908284
2020 Regulation of CD47 expression in cancer cells. Translational oncology 86 32920329
2019 Inhibitor of Apoptosis Protein (IAP) Antagonists in Anticancer Agent Discovery: Current Status and Perspectives. Journal of medicinal chemistry 84 30676015
2004 Promotion of neurite and filopodium formation by CD47: roles of integrins, Rac, and Cdc42. Molecular biology of the cell 83 15215311
2003 Inhibitor of apoptosis protein (IAP) survivin is upregulated by oncogenic c-H-Ras. Oncogene 82 12833149
2012 CD47 deficiency confers cell and tissue radioprotection by activation of autophagy. Autophagy 81 22874555
2004 Role of CD47 in erythroid cells and in autoimmunity. Leukemia & lymphoma 80 15359629
2021 Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine. International journal of molecular sciences 78 33920030
2020 Just eat it: A review of CD47 and SIRP-α antagonism. Seminars in oncology 73 32517874
2019 Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment. Computational and structural biotechnology journal 71 30766663
2019 Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment. Cell death & disease 70 30814491
2018 Regulation of innate and adaptive antitumor immunity by IAP antagonists. Immunotherapy 70 29807457
2010 Small-molecule pan-IAP antagonists: a patent review. Expert opinion on therapeutic patents 67 20100005
2007 Livin/ML-IAP as a new target for cancer treatment. Cancer letters 66 17218055
2011 Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity. Discovery medicine 62 21447281
2014 Smac mimetics as IAP antagonists. Seminars in cell & developmental biology 61 25550219
2019 Checkpoint CD47 Function On Tumor Metastasis And Immune Therapy. OncoTargets and therapy 59 31806995
2017 Smac Mimetics to Therapeutically Target IAP Proteins in Cancer. International review of cell and molecular biology 59 28215531
2002 Reaper is regulated by IAP-mediated ubiquitination. The Journal of biological chemistry 58 12446669
2023 SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis. The Journal of clinical investigation 54 36626230
2023 EGFR-Induced and c-Src-Mediated CD47 Phosphorylation Inhibits TRIM21-Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 54 37541303
2014 Inhibitor of Apoptosis (IAP) proteins in hematological malignancies: molecular mechanisms and therapeutic opportunities. Leukemia 52 24487414
2014 Triggering necroptosis in cisplatin and IAP antagonist-resistant ovarian carcinoma. Cell death & disease 52 25356865
2021 Overlap of NatA and IAP substrates implicates N-terminal acetylation in protein stabilization. Science advances 51 33523899
2014 Thrombospondin-1 and CD47 signaling regulate healing of thermal injury in mice. Matrix biology : journal of the International Society for Matrix Biology 51 24840925
2022 Role of CD47 in tumor immunity: a potential target for combination therapy. Scientific reports 50 35697717
2004 Identification and functional analysis of Hyphantria cunea nucleopolyhedrovirus iap genes. Virology 50 15051395
1992 A new octopamine receptor class in locust nervous tissue, the octopamine 3 (OA3) receptor. Life sciences 49 1345878
2023 A nanodrug combining CD47 and sonodynamic therapy efficiently inhibits osteosarcoma deterioration. Journal of controlled release : official journal of the Controlled Release Society 48 36682726
2012 IAP proteins: regulators of cell migration and development. Current opinion in cell biology 48 23219152
2023 Deciphering the role of CD47 in cancer immunotherapy. Journal of advanced research 45 39167629
2021 Antibody:CD47 ratio regulates macrophage phagocytosis through competitive receptor phosphorylation. Cell reports 44 34433055
2007 Evaluation of an ovine testis cell line (OA3.Ts) for propagation of capripoxvirus isolates and development of an immunostaining technique for viral plaque visualization. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 44 17823391
2001 Cloning and characterization of an inhibitor of apoptosis protein (IAP) from Bombyx mori. Biochimica et biophysica acta 44 11341966
2021 Cancer Therapy Targeting CD47/SIRPα. Cancers 43 34944850
2014 Synergistic effects of IAP inhibitor LCL161 and paclitaxel on hepatocellular carcinoma cells. Cancer letters 42 24976294
2019 Stealth functionalization of biomaterials and nanoparticles by CD47 mimicry. International journal of pharmaceutics 41 31421198
2020 IAP-Mediated Protein Ubiquitination in Regulating Cell Signaling. Cells 40 32365919
2004 Cholesterol-independent interactions with CD47 enhance alphavbeta3 avidity. The Journal of biological chemistry 37 14966135
2000 The IAP proteins: caspase inhibitors and beyond. Science's STKE : signal transduction knowledge environment 37 11752601
2018 Anticancer effects of anti-CD47 immunotherapy in vivo. Oncoimmunology 36 30723582
2020 Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition. mBio 35 32576678
2010 Implication of the CD47 pathway in autoimmune diabetes. Journal of autoimmunity 35 20138735
2012 Inhibitor of Apoptosis (IAP) proteins as therapeutic targets for radiosensitization of human cancers. Cancer treatment reviews 34 22342104
2020 Blocking thrombospondin-1 signaling via CD47 mitigates renal interstitial fibrosis. Laboratory investigation; a journal of technical methods and pathology 32 32366943
2019 Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy. Pathobiology : journal of immunopathology, molecular and cellular biology 32 31132784
2005 Novel CD47-dependent intercellular adhesion modulates cell migration. Journal of cellular physiology 32 15880429
2014 Brain CD47 expression in a swine model of intracerebral hemorrhage. Brain research 31 24931767
2004 Neuronal roles of the integrin-associated protein (IAP/CD47) in developing cortical neurons. The Journal of biological chemistry 31 15297459
2022 Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis. Molecular pharmaceutics 30 35436123
2018 Insights into CD47/SIRPα axis-targeting tumor immunotherapy. Antibody therapeutics 30 34056543
2017 IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells. Cancer immunology research 30 29187357
2014 IAP gene deletion and conditional knockout models. Seminars in cell & developmental biology 30 25545814
2022 Advantage of extracellular vesicles in hindering the CD47 signal for cancer immunotherapy. Journal of controlled release : official journal of the Controlled Release Society 29 36162554
2021 Modulation of CD47-SIRPα innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody. Cancer immunology, immunotherapy : CII 29 34247273
2022 CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals. eLife 28 36454036
2016 Enhanced biocompatibility of CD47-functionalized vascular stents. Biomaterials 28 26914699
2006 Target cell CD47 regulates macrophage activation and erythrophagocytosis. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 28 16564725
2017 Significance of CD47 expression in gastric cancer. Oncology letters 27 28693236
2021 Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer. Molecular cancer therapeutics 26 34389694
2020 Clinicopathological significance of CD47 expression in hepatocellular carcinoma. Journal of clinical pathology 26 32576628
2013 Pertussis vaccines: position paper of Indian Academy of Pediatrics (IAP). Indian pediatrics 26 24382899