Browse CD47

Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Multi-pass membrane protein
Domain PF04549 CD47 transmembrane region
PF08204 CD47 immunoglobulin-like domain
Function

Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells. May be involved in membrane permeability changes induced following virus infection.

> Gene Ontology
 
Biological Process GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0006909 phagocytosis
GO:0007159 leukocyte cell-cell adhesion
GO:0007229 integrin-mediated signaling pathway
GO:0008228 opsonization
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030100 regulation of endocytosis
GO:0030198 extracellular matrix organization
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0042110 T cell activation
GO:0043062 extracellular structure organization
GO:0045785 positive regulation of cell adhesion
GO:0045807 positive regulation of endocytosis
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050764 regulation of phagocytosis
GO:0050766 positive regulation of phagocytosis
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050900 leukocyte migration
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0060627 regulation of vesicle-mediated transport
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071593 lymphocyte aggregation
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
Molecular Function GO:0070053 thrombospondin receptor activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04512 ECM-receptor interaction
Reactome R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-1500931: Cell-Cell communication
R-HSA-1474244: Extracellular matrix organization
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-216083: Integrin cell surface interactions
R-HSA-6798695: Neutrophil degranulation
R-HSA-391160: Signal regulatory protein (SIRP) family interactions
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CD47 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CD47 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28153099LymphomaInhibit immunityCD47 interacts with its counter-receptor SIRPα on macrophages and other myeloid cells to inhibit cancer cell phagocytosis and drive immune evasion.
27035983Pancreatic Neuroendocrine TumorInhibit immunityWe performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a "don't eat me" signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed.
26966191Leukemia; LymphomaInhibit immunity (T cell function)MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response.
26322579Colon AdenocarcinomaInhibit immunity (T cell function)Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.
26116271Pan-CancerInhibit immunity (T cell function)Blockade of the CD47:SIRP-α axis between tumor cells and innate immune cells (monocytes, macrophages, and dendritic cells) increases tumor cell phagocytosis in both solid tumors (including, but not limited to, bladder, breast, colon, lung, and pancreatic) and hematologic malignancies.
25697354Lung CarcinomaInhibit immunityExogenous treatment of TSP-1 may be able to suppress the CD47-mediated tumor immune escape by disrupting the CD47-SIRP-a interaction. With the increasing surface expression of CD47, this suppression effect may be even more obvious in immune-selected cells. These findings prove that the TSP-1/CD47/SIRP-α signal axis is important to the evolution of tumor cells in the microenvironment of immunotherapy and identify thrombospondin-1 as a key signal with therapeutic benefits in overcoming long term relapse, providing new evidence for the clinical promise of cancer vaccination.
25297630MelanomaInhibit immunityCorrespondingly, an inverse correlation between CD8(+) T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8(+) cytotoxic T cells, with the potential to increase curative responses.
27569584Ovarian CarcinomaInhibit immunityThe CD47 "don't eat me signal" is highly expressed in human ovarian cancer. The CD47 "don't eat me" signal allows tumor immune evasion. This demonstrates that while CD47 may be an immunologic shield that may be considered for targeted therapies, it is likely that it operates in concert with other mechanisms of immune evasion.
29368647T Acute Lymphoblastic LeukemiaInhibit immunityMIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47. Functional studies showed that restoration of miR-708 expression in the T-ALL cell line is sufficient to promote phagocytosis by macrophages in the absence or presence of the anti-CD47 antibody to eradicate T-ALL cells, and inhibited tumor engraftment in vivo.
29288236Pancreatic CarcinomaInhibit immunityCD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer. Immunohistochemistry and flow cytometry were used to measure CD47 ("don't eat me signal") expression on tumor cells and characterize macrophages in the tumor microenvironment. Treatment of mice with CD47-blocking antibodies resulted in increased time-to-progression of metastatic tumors and prolonged survival. These findings suggest that following surgical resection of PDAC, adjuvant immunotherapy with anti-CD47 antibody could lead to substantially improved outcomes for patients.
28723893MelanomaInhibit immunity; decrease the efficacy of immunotherapyTo confirm that CD47null tumours were more susceptible to GVAX and PD-1 blockade, we generated CD47-null B16 melanoma cells using transient transfection of a Cas9-sgRNA plasmid (Extended Data Fig. 2a) and found that loss of CD47 significantly improved control of tumour growth mediated by GVAX and anti-PD-1 immunotherapy (Extended Data Fig. 2b, P < 0.01). Therefore, in vivo genetic screening recovered genes known to confer immune evasion properties on cancer cells.
27294525Small cell lung carcinomaInhibit immunityCD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages.?In a murine model, administration of CD47-blocking antibodies or targeted inactivation of the Cd47 gene markedly inhibited SCLC tumor growth.
28465453Lung CarcinomaInhibit immunityIn this issue ofCancer Immunology Research, Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway.
21178137Bladder CarcinomaInhibit immunityHere, we identified calreticulin as a pro-phagocytic signal that was highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells. Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis.
21177380Acute Lymphoblastic LeukemiaInhibit immunityCD47 was found to be more highly expressed on a subset of human ALL patient samples compared with normal cell counterparts and to be an independent predictor of survival and disease refractoriness in several ALL patient cohorts. In addition, a blocking monoclonal antibody against CD47 enabled phagocytosis of ALL cells by macrophages in vitro and inhibited tumor engraftment in vivo.
22451919LeiomyosarcomaInhibit immunity (T cell function); immunotherapy targetAntibodies against CD47, which block tumor cell CD47 interactions with macrophage signal regulatory protein-α, have been shown to decrease tumor size in hematological and epithelial tumor models by interfering with the protection from phagocytosis by macrophages that intact CD47 bestows upon tumor cells.
22451913Breast CarcinomaInhibit immunity (T cell function); immunotherapy targetIn vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected.? These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.
28378740Breast CarcinomaInhibit immunityWe identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. These results suggest that cancers can evolve SE to drive CD47 overexpression to escape immune surveillance.
24726056Primary Effusion LymphomaInhibit immunityKnocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice.
29632713breast carcinomaInhibit immunityThese results provide a rationale for an innovative preclinical combination immunotherapy based on PD-1/PD-L1 and CD47 blockade along with EMT inhibitors in patients with highly aggressive, mesenchymal, and metastatic breast cancer.
29308321GliomaInhibit immunityWe next examined the effects of anti-CD47 antibody on glioma cells/GSCs in an immune competent mouse glioma model, revealing significant inhibition of tumor growth and prolonged survival times. In summary, we have shown that CD47 is a potentially safe and effective therapeutic target for glioma.
28874561MelanomaInhibit immunity; Resistant to immunotherapyCD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Generation of a B16F10 cell line that secretes the A4 nanobody showed that an enhanced response to several immune therapies requires near-complete blockade of CD47 in the tumor microenvironment.
28801234Colon AdenocarcinomaInhibit immunityHere we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol, contributing to type I interferon (IFN) production and antitumor adaptive immunity.
23292955Head and Neck Squamous Cell CarcinomaInhibit immunityFinally, decreasing tumor cell CD47 in combination with standard radiation and chemotherapy results in improved immune-mediated tumor clearance in vivo.
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CD47 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 5.03; FDR: 0.002 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX STARS Score: 4.84; FDR: 0.005 Resistant to T cell-mediated killing
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CD47 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.240.303
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.3280.887
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1820.909
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.170.811
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2280.941
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.680.855
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0830.857
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.030.988
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1980.929
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4750.798
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3410.907
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1360.178
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CD47 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)2117011.8-11.80.193
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)1311018.2-18.20.199
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD47. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD47. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD47.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD47. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CD47 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CD47 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCD47
NameCD47 molecule
Aliases antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location3q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CD47 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.