TISIDB

Summary
Symbol	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
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 I membrane protein
Domain	PF07686 Immunoglobulin V-set domain
Function	May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling.

> Gene Ontology [ TOP ]
Biological Process	GO:0001503 ossification GO:0001649 osteoblast differentiation GO:0001818 negative regulation of cytokine production GO:0001819 positive regulation of cytokine production 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:0030278 regulation of ossification GO:0030282 bone mineralization GO:0030500 regulation of bone mineralization GO:0030501 positive regulation of bone mineralization GO:0031214 biomineral tissue development GO:0031348 negative regulation of defense response GO:0032102 negative regulation of response to external stimulus GO:0032609 interferon-gamma production GO:0032623 interleukin-2 production GO:0032649 regulation of interferon-gamma production GO:0032663 regulation of interleukin-2 production GO:0032689 negative regulation of interferon-gamma production GO:0032703 negative regulation of interleukin-2 production GO:0032729 positive regulation of interferon-gamma production GO:0032743 positive regulation of interleukin-2 production GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032945 negative regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0042035 regulation of cytokine biosynthetic process GO:0042036 negative regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042094 interleukin-2 biosynthetic process GO:0042095 interferon-gamma biosynthetic process GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0042130 negative regulation of T cell proliferation GO:0045072 regulation of interferon-gamma biosynthetic process GO:0045076 regulation of interleukin-2 biosynthetic process GO:0045077 negative regulation of interferon-gamma biosynthetic process GO:0045078 positive regulation of interferon-gamma biosynthetic process GO:0045085 negative regulation of interleukin-2 biosynthetic process GO:0045667 regulation of osteoblast differentiation GO:0045669 positive regulation of osteoblast differentiation GO:0045778 positive regulation of ossification 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:0050672 negative 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:0050727 regulation of inflammatory response GO:0050728 negative regulation of inflammatory response 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:0070167 regulation of biomineral tissue development GO:0070169 positive regulation of biomineral tissue development GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070664 negative regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0070970 interleukin-2 secretion GO:0071593 lymphocyte aggregation 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	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD276 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 CD276 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
22547582	Chronic Lymphocytic Leukemia	Inhibit immunity	In the present study, we show via functional screening assays that CD200, CD270, CD274, and CD276 are coopted by CLL cells to induce impaired actin synapse formation in both allogeneic and autologous T cells.
19584290	Neuroblastoma	Inhibit immunity (T cell function)	B7-H3 protein expression was inversely correlated with miR-29 levels in both cell lines and tumor tissues tested. Using luciferase reporter assay, miR-29a was shown to directly target B7-H3 3' untranslated region, and knock-in and knockdown of miR-29a led to down-regulation and up-regulation, respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3 protein expression has implications in immune escape by solid tumors.
19844235	Pancreatic Carcinoma	Inhibit immunity (infiltration)	B7-H3 blockade promoted CD8(+) T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer.
24013874	Malignant Central Nervous System Neoplasm	Inhibit immunity (infiltration)	B7-H3 (CD276), a newly identified member of the B7 family of molecules, is often induced in human tumors and its overexpression is closely correlated with survival, prognosis or tumor grade. Despite ample evidence implicating B7-H3 in tumor immune escape, a steady flow of reports have suggested that it may also have antitumor effects under certain circumstances. The safety and efficacy of targeting B7-H3 with a monoclonal antibody for the treatment of advanced-stage central nervous system cancer in children has been proven, making B7-H3 an attractive therapeutic target for this kind of tumor. In addition, B7-H3 was shown to promote invasion and accelerate carcinogenesis in tumor progression according to its nonimmunological regulatory roles.
29530936	Non-Small Cell Lung Carcinoma	Inhibit immunity (T cell function)	B7-H3 negatively modulates CTL-mediated cancer immunity. B7-H3 expressed on tumor cells potentially circumvents CD8+-T-cell-mediated immune surveillance.
28685773	Lymphoma; Melanoma	Inhibit immunity (T cell function)	Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice.
22080438	Glioma	Inhibit immunity	B7H3 expression by tumor and endothelial cells correlates with the grade of malignancy in gliomas and with poor survival. Both soluble 4IgB7H3 in the supernatant of glioma cells and cell-bound 4IgB7H3 are functional and suppress natural killer cell-mediated tumor cell lysis
21597388	Non-Small Cell Lung Carcinoma	Inhibit immunity	Non-small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B7-H3. B7-H3 was significantly upregulated in tumor-residing DC, whereas the expression of other B7 molecules, such as B7-DC, B7-1, B7-2, B7-H1, remained unchanged. Significantly reduced levels of T cell proliferation in mixed lymphocyte reactions with tumor-derived DC were recorded. Moreover, elevated concentrations of IL-10 were measured in tumor-derived DC, whereas IL-12 levels were reduced.
20495537	Ovarian Carcinoma	Inhibit immunity	Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P=0.02) and a higher incidence of recurrence (P=0.03). These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival.
21982044	Endometrial Carcinoma	Inhibit immunity(infiltration)	B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor.

Summary
Symbol	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
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 CD276 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	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
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 CD276 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	-0.374	0.255
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.284	0.917
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.437	0.824
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.299	0.641
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.603	0.787
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.093	0.975
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.153	0.758
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.636	0.736
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.402	0.845
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.595	0.764
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	1.09	0.706
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.151	0.106

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD276 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	1.4	2.3	0.469
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	1.7	2	0.532
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	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD276. 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	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD276. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD276. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD276. 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	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD276 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD276 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD276
Name	CD276 molecule
Aliases	B7-H3; B7H3; B7RP-2; CD276 antigen; 4Ig-B7-H3; B7 homolog 3; costimulatory molecule; CD antigen CD276
Chromosomal Location	15q23-q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD276 collected from DrugBank database.

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

Browse CD276