TISIDB

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
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	Membrane Multi-pass membrane protein
Domain	PF01150 GDA1/CD39 (nucleoside phosphatase) family
Function	In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well.

> Gene Ontology [ TOP ]
Biological Process	GO:0007596 blood coagulation GO:0007599 hemostasis GO:0050817 coagulation GO:0050878 regulation of body fluid levels
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00230 Purine metabolism hsa00240 Pyrimidine metabolism
Reactome	R-HSA-1430728: Metabolism R-HSA-15869: Metabolism of nucleotides R-HSA-8850843: Phosphate bond hydrolysis by NTPDase proteins

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ENTPD1 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 ENTPD1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27245613	Cervical Carcinoma	Inhibit immunity	PKA also stimulated the binding of the coactivator p300 to HIF-1α to enhance its transcriptional activity and counteracted the inhibitory effect of asparaginyl hydroxylation on the association of p300 with HIF-1α. Furthermore, increased cAMP concentrations enhanced the expression of HIF target genes encoding CD39 and CD73, which are enzymes that convert extracellular adenosine 5'-triphosphate to adenosine, a molecule that enhances tumor immunosuppression and reduces heart rate and contractility.
25971300	Glioblastoma	Inhibit immunity (T cell function)	FGL2 augments glioma immunosuppression by increasing the expression levels of PD-1 and CD39, expanding the frequency of tumor-supportive M2 macrophages via the FcγRIIB pathway, and enhancing the number of MDSCs and CD39(+) regulatory T cells.
25403716	Melanoma	Inhibit immunity (T cell function)	The generation of adenosine via the CD39/CD73 pathway is recognized as a major mechanism of regulatory T cell (Treg) immunosuppressive function. Blockade of CD39 increases CTL- and NK cell–mediated killing.
29375567	Ovarian Carcinoma	Inhibit immunity	Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer. Metformin triggered activation of AMP-activated protein kinase α (AMPKα) and subsequently suppressed hypoxia-inducible factor-α (HIF-1α), which was critical for induction of CD39/CD73 expression in MDSC.
29374065	Ovarian Carcinoma	Inhibit immunity (T cell function); immunotherapy target	Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.
27321181	Ovarian carcinoma	Inhibit immunity	Adenosine is a major determinant of the immunosuppressive tumor milieu. Sequential hydrolysis of extracellular ATP catalyzed by CD39 and CD73 is the main pathway for the generation of adenosine in the tumor interstitium.
23737488	Malignant Glioma	Inhibit immunity (T cell function)	We demonstrated that increased suppression of responder CD4(+) T-cell proliferation suppression was induced by CD4(+)CD39(+) T cells in the presence of CD73(+) glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. Our data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4(+)CD39(+) T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.
19864600	Follicular Lymphoma	Inhibit immunity	As the rate limiting step for adenosine generation from pericellular ATP is the ecto-ATPase CD39, we next show that inhibition of CD39 activity using the inhibitor ARL 67156 partially overcomes T cell hyporesponsiveness in a subset of patient samples.
19825957	Head and Neck Carcinoma	Inhibit immunity (T cell function)	The percentages and expression levels of CD39 and CD73 in CD4(+) T cells and Treg were greater in HNSCC than in normal controls and highest in patients with no evident disease. Patients' Treg hydrolyzed ATP at higher rates and produced higher levels of adenosine than normal controls' Treg. The increased frequency and enzymatic activity of CD4(+)CD39(+) cells corresponded to increased adenosine-mediated suppression of effector T cells, which was partly inhibited by ARL67156, an ectonucleotidase inhibitor, and by ZM241385, a selective A(2a)/A(2b) receptor antagonist.
20546740	Melanoma	Inhibit immunity (T cell function)	We demonstrate that hepatic growth of melanoma metastatic tumors was strongly inhibited in mice with Cd39 null vasculature or in wt mice with circulating Cd39 null bone marrow-derived cells. We show functional CD39 expression on CD4(+)Foxp3(+) Tregs suppressed antitumor immunity mediated by natural killer (NK) cells in vitro and in vivo. CD39 expression on Tregs inhibits NK activity and is permissive for metastatic growth.
25205101	melanoma	Inhibit immunity	However, current protocols for ex vivo programming of Th17 cells, which include TGFbeta exposure, increase the expression of CD39 and CD73, two cell surface ATP ectonucleotidases that reduce T-cell effector functions and promote immunosuppression

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
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 ENTPD1 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	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 3	Resistant to T-cell proliferation

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
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 ENTPD1 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	0.073	0.826
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.335	0.8
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.119	0.906
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.082	0.844
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.284	0.919
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.174	0.961
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.233	0.559
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.658	0.702
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.276	0.889
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.148	0.416
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	1.841	0.404
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.272	0.024

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ENTPD1 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	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
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	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ENTPD1. 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	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ENTPD1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ENTPD1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ENTPD1. 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	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ENTPD1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ENTPD1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Aliases	NTPDase-1; ATPDase; SPG64; CD39; CD39 antigen; NTPDase 1; ecto-ATP diphosphohydrolase 1; ecto-ATPDase 1; ect ......
Chromosomal Location	10q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ENTPD1 collected from DrugBank database.

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

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