TISIDB

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
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; Single-pass type II membrane protein.
Domain	PF00229 TNF(Tumour Necrosis Factor) family
Function	Cytokine that binds to CD27. Plays a role in T-cell activation. Induces the proliferation of costimulated T-cells and enhances the generation of cytolytic T-cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034612 response to tumor necrosis factor GO:0071356 cellular response to tumor necrosis factor GO:0097191 extrinsic apoptotic signaling pathway
Molecular Function	GO:0002020 protease binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005164 tumor necrosis factor receptor binding GO:0032813 tumor necrosis factor receptor superfamily binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-5669034: TNFs bind their physiological receptors

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD70 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 CD70 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24569779	B-Cell Non-Hodgkin Lymphoma	Inhibit immunity (T cell function)	TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin's lymphoma.
16751420	Melanoma	Promote immunity (T cell function)	Incubation in vitro with high doses of IL-2 (3,000 IU/ml) or administration of IL-2 in vivo resulted in substantial up-regulation of CD70 expression and the concomitant loss of cell surface CD27 expression on CD8(+) cells. Withdrawal of IL-2 from activated CD8(+) T cells that had been maintained in IL-2 resulted in a reversal of the expression of these two markers, whereas reciprocal changes were seen following treatment of PBMCs with IL-2. The proliferation observed in cells stimulated with IL-2 primarily occurred in a subset of the CD70(+)CD8(+) T cells that up-regulated IL-2 receptor expression but did not occur in CD70(-)CD8(+) T cells. Blocking CD70 resulted in a significant reduction of T cell proliferation induced by high-dose IL-2, indicating that the interaction of CD70 with CD27 played a direct role in T cell activation mediated by IL-2. Finally, studies conducted on tumor-infiltrating lymphocyte (TIL) samples that were administered to melanoma patients indicated that the size of the pool of CD27(+)CD8(+) T cells in bulk TILs was highly associated (p = 0.004) with the ability of these TILs to mediate tumor regression following adoptive transfer.
19109206	Leukemia	Promote immunity (T cell function)	Both CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary stimulation of T cell proliferation and cytokine production in an additive manner. These two signals also cooperate in the prevention of T cell anergy. In contrast to blockade of CD70 during the effector phase, inhibition of CD70-mediated costimulation during generation of antileukemic T cells prevents effector cell proliferation and reduces their cytotoxic capacity.
23904461	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic.
15958592	Glioblastoma	Inhibit immunity	Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by promoting T-cell death via tumor-associated CD70 and gangliosides that act through receptor-dependent and receptor-independent pathways, respectively. Our results indicate that CD70 and gangliosides are both products synthesized by GBMs that may be key mediators of T-cell apoptosis and likely contribute to the T-cell dysfunction observed within the tumor microenvironment.
28651374	Glioma	Inhibit immunity	CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death.
28612394	Glioblastoma	Inhibit immunity	Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation.
28011863	Hodgkin Lymphoma	Promote immunity	Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection. We show that EBV-specific T lymphocytes did not expand properly when stimulated with CD70-deficient EBV-infected B cells, whereas expression of CD70 in B cells restored expansion, indicating that CD70 on B cells but not on T cells is required for efficient proliferation of T cells.
16217761	Glioma	Promote immunity	Immune stimulatory effects of CD70 override CD70-mediated immune cell apoptosis in rodent glioma models and confer long-lasting antiglioma immunity in vivo. In nude mice, CD70 expression in SMA-560 gliomas delays the glioma growth upon subcutaneous (s.c.) or intracerebral (i.c.) inoculation, suggesting a role for CD70/CD27-dependent NK cell activity in tumor surveillance. Similarly, CD70-expressing GL-261 gliomas are rejected in syngeneic C57BL/6 mice, while glioma growth is restored in C57BL/6 CD27(-/-) mice, suggesting that the CD70/CD27 interaction recruits a tumor-specific T-cell repertoire and induces tumor-specific memory.

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
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 CD70 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	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
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 CD70 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	-0.498	0.415
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.216	0.286
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.026	0.978
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.529	0.462
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.427	0.702
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.666	0.592
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.478	0.466
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.754	0.452
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.2	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.638	0.197
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	2.787	0.345
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.098	0.715

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD70 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	1

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD70. 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	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD70. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD70. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD70. 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	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD70 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD70 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD70
Name	CD70 molecule
Aliases	CD27L; CD27LG; TNFSF7; tumor necrosis factor (ligand) superfamily, member 7; CD27 ligand; CD27-L; Ki-24 anti ......
Chromosomal Location	19p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD70 collected from DrugBank database.

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

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