TISIDB

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
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 Single-pass type I membrane protein Note=Expressed at the cell surface. A soluble form has also been detected.
Domain	PF07686 Immunoglobulin V-set domain
Function	Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation.

> Gene Ontology [ TOP ]
Biological Process	GO:0001562 response to protozoan GO:0001819 positive regulation of cytokine production GO:0002250 adaptive immune response GO:0002683 negative regulation of immune system process GO:0002694 regulation of leukocyte activation GO:0002695 negative regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0007159 leukocyte cell-cell adhesion GO:0007162 negative regulation of cell adhesion GO:0009306 protein secretion GO:0022407 regulation of cell-cell adhesion GO:0022408 negative regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0032609 interferon-gamma production GO:0032623 interleukin-2 production GO:0032633 interleukin-4 production GO:0032663 regulation of interleukin-2 production GO:0032743 positive regulation of interleukin-2 production GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0045785 positive regulation of cell adhesion GO:0046651 lymphocyte proliferation GO:0050663 cytokine secretion GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050868 negative regulation of T cell activation GO:0050870 positive regulation of T cell activation GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051249 regulation of lymphocyte activation GO:0051250 negative regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0070970 interleukin-2 secretion GO:0071593 lymphocyte aggregation GO:0072602 interleukin-4 secretion GO:0072643 interferon-gamma secretion GO:1900040 regulation of interleukin-2 secretion GO:1900042 positive regulation of interleukin-2 secretion GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903038 negative regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization
Molecular Function	-
Cellular Component	GO:0009897 external side of plasma membrane GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04514 Cell adhesion molecules (CAMs)
Reactome	-

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between VTCN1 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 VTCN1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27001312	Glioma	Inhibit immunity (T cell function)	Mechanistically, glioma initiating CD133(+) cells and Mφs/microglia cointeraction activated expression of B7-H4 via IL6 and IL10 in both tumor cells and microenvironment supporting cells. IL6-activated STAT3 bound to the promoter of B7-H4 gene and enhanced B7-H4 expression. Furthermore, CD133(+) cells mediated immunosuppression through B7-H4 expression on Mφs/microglia by silencing of B7-H4 expression on these cells, which led to increased microenvironment T-cell function and tumor regression in the xenograft glioma mouse model.
29374053	Non-Small Cell Lung Carcinoma	Inhibit immunity (T cell function)	We demonstrated that HHLA2, a newly identified immune inhibitory molecule, was widely expressed in NSCLC. The triple-positive group had more TIL infiltration than the triple-negative group. B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation of CD4 and CD8 T cells more robustly than PD-L1-Ig. All three significantly suppressed cytokine productions by T cells.
24657487	Malignant Female Reproductive System Neoplasm	Inhibit immunity (T cell function); immunotherapy target	B7-H4 as a potential target for immunotherapy for gynecologic cancers: a closer look. B7-H4 is a transmembrane protein that binds an unknown receptor on activated T cells resulting in inhibition of T-cell effector function via cell cycle arrest, decreased proliferation, and reduced IL-2 production.
23722540	Ovarian Carcinoma	Inhibit immunity (T cell function); immunotherapy target	We identified anti-B7-H4 scFv that reversed in vitro inhibition of CD3-stimulated T cells by B7-H4 protein. Notably, these reagents rescued tumor antigen-specific T-cell activation, which was otherwise inhibited by coculture with antigen-loaded B7-H4+ APCs, B7-H4+ tumor cells, or B7-H4- tumor cells mixed with B7-H4+ TAMs; peritoneal administration of anti-B7-H4 scFv delayed the growth of established tumors.
29625896	hepatocellular carcinoma	Inhibit immunity (T cell function); decrease the efficacy of immunotherapy	Collectively, B7S1 initiates dysfunction of tumor-infiltrating CD8+ T cells and may be targeted for cancer immunotherapy.
21378130	Melanoma	Inhibit immunity (T cell function)	The numbers of CD68(+) macrophages were significantly lower in patients with low B7-H4 expression, whereas CD8(+) T-cell infiltrates were independent of expression levels. Overexpression of B7-H4 on melanoma cells did not alter the cytotoxicity of different CD8(+) effector cells, but drastically inhibited cytokine production. Our study provides for the first time evidence of B7-H4 expression on melanoma cells as a mechanism controlling tumor immunity which is associated with patients' survival.
18676826	Renal Cell Carcinoma	Inhibit immunity	B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome.
29872577	Lung Carcinoma	Inhibit immunity	TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner.
17509674	Endometrioid Adenocarcinoma	Inhibit immunity (infiltration)	B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration. The proportion of B7-H4 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive tumor-associated lymphocytes (TALs).

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
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 VTCN1 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	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
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 VTCN1 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	0.306	0.161
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.096	0.841
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.605	0.167
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.236	0.784
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.441	0.337
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.281	0.46
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.965	0.204
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.905	0.199
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.1	0.946
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.004	0.996
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	0.711	0.459
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.061	0.875

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of VTCN1 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
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	0	0	0	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	0	0	0	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	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of VTCN1. 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	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of VTCN1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by VTCN1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of VTCN1. 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	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of VTCN1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between VTCN1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	VTCN1
Name	V-set domain containing T cell activation inhibitor 1
Aliases	B7-H4; FLJ22418; B7S1; B7X; B7H4; B7 family member, H4; B7 superfamily member 1; B7h.5; PRO1291; VCTN1; B7 h ......
Chromosomal Location	1p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting VTCN1 collected from DrugBank database.

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

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