TISIDB

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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

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Literatures describing the relation between CD47 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28153099	Lymphoma	Inhibit immunity	CD47 interacts with its counter-receptor SIRPα on macrophages and other myeloid cells to inhibit cancer cell phagocytosis and drive immune evasion.
27035983	Pancreatic Neuroendocrine Tumor	Inhibit immunity	We 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.
26966191	Leukemia; Lymphoma	Inhibit immunity (T cell function)	MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response.
26322579	Colon Adenocarcinoma	Inhibit immunity (T cell function)	Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.
26116271	Pan-Cancer	Inhibit 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.
25697354	Lung Carcinoma	Inhibit immunity	Exogenous 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.
25297630	Melanoma	Inhibit immunity	Correspondingly, 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.
27569584	Ovarian Carcinoma	Inhibit immunity	The 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.
29368647	T Acute Lymphoblastic Leukemia	Inhibit immunity	MIR-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.
29288236	Pancreatic Carcinoma	Inhibit immunity	CD47 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.
28723893	Melanoma	Inhibit immunity; decrease the efficacy of immunotherapy	To 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.
27294525	Small cell lung carcinoma	Inhibit immunity	CD47 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.
28465453	Lung Carcinoma	Inhibit immunity	In 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.
21178137	Bladder Carcinoma	Inhibit immunity	Here, 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.
21177380	Acute Lymphoblastic Leukemia	Inhibit immunity	CD47 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.
22451919	Leiomyosarcoma	Inhibit immunity (T cell function); immunotherapy target	Antibodies 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.
22451913	Breast Carcinoma	Inhibit immunity (T cell function); immunotherapy target	In 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.
28378740	Breast Carcinoma	Inhibit immunity	We 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.
24726056	Primary Effusion Lymphoma	Inhibit immunity	Knocking 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.
29632713	breast carcinoma	Inhibit immunity	These 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.
29308321	Glioma	Inhibit immunity	We 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.
28874561	Melanoma	Inhibit immunity; Resistant to immunotherapy	CD47 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.
28801234	Colon Adenocarcinoma	Inhibit immunity	Here 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.
23292955	Head and Neck Squamous Cell Carcinoma	Inhibit immunity	Finally, decreasing tumor cell CD47 in combination with standard radiation and chemotherapy results in improved immune-mediated tumor clearance in vivo.

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 5.03; FDR: 0.002	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.84; FDR: 0.005	Resistant to T cell-mediated killing
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.24	0.303
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.328	0.887
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.182	0.909
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.17	0.811
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.228	0.941
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.68	0.855
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.083	0.857
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.03	0.988
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.198	0.929
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.475	0.798
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.341	0.907
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.136	0.178

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	18.2	-18.2	0.199
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-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 [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD47
Name	CD47 molecule
Aliases	antigen identified by monoclonal antibody 1D8; antigenic surface determinant protein OA3; integrin associate ......
Chromosomal Location	3q13.1-q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD47 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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