TISIDB

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
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	Isoform Alpha: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform Delta: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform Beta: Secreted.; SUBCELLULAR LOCATION: Isoform Gamma: Secreted.
Domain	PF08205 CD80-like C2-set immunoglobulin domain PF07686 Immunoglobulin V-set domain
Function	Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. ; FUNCTION: (Microbial infection) Acts as a receptor for poliovirus. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport. ; FUNCTION: (Microbial infection) Acts as a receptor for Pseudorabies virus. ; FUNCTION: (Microbial infection) Is prevented to reach cell surface upon infection by Human cytomegalovirus /HHV-5, presumably to escape immune recognition of infected cell by NK cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0001906 cell killing GO:0001909 leukocyte mediated cytotoxicity GO:0001910 regulation of leukocyte mediated cytotoxicity GO:0001912 positive regulation of leukocyte mediated cytotoxicity GO:0001913 T cell mediated cytotoxicity GO:0001914 regulation of T cell mediated cytotoxicity GO:0001916 positive regulation of T cell mediated cytotoxicity GO:0002228 natural killer cell mediated immunity GO:0002250 adaptive immune response GO:0002347 response to tumor cell GO:0002418 immune response to tumor cell GO:0002420 natural killer cell mediated cytotoxicity directed against tumor cell target GO:0002423 natural killer cell mediated immune response to tumor cell GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002456 T cell mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002697 regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002703 regulation of leukocyte mediated immunity GO:0002705 positive regulation of leukocyte mediated immunity GO:0002706 regulation of lymphocyte mediated immunity GO:0002708 positive regulation of lymphocyte mediated immunity GO:0002709 regulation of T cell mediated immunity GO:0002711 positive regulation of T cell mediated immunity GO:0002715 regulation of natural killer cell mediated immunity GO:0002717 positive regulation of natural killer cell mediated immunity GO:0002819 regulation of adaptive immune response GO:0002821 positive regulation of adaptive immune response GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002831 regulation of response to biotic stimulus GO:0002833 positive regulation of response to biotic stimulus GO:0002834 regulation of response to tumor cell GO:0002836 positive regulation of response to tumor cell GO:0002837 regulation of immune response to tumor cell GO:0002839 positive regulation of immune response to tumor cell GO:0002855 regulation of natural killer cell mediated immune response to tumor cell GO:0002857 positive regulation of natural killer cell mediated immune response to tumor cell GO:0002858 regulation of natural killer cell mediated cytotoxicity directed against tumor cell target GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0008037 cell recognition GO:0019058 viral life cycle GO:0030260 entry into host cell GO:0031341 regulation of cell killing GO:0031343 positive regulation of cell killing GO:0031349 positive regulation of defense response GO:0034330 cell junction organization GO:0034332 adherens junction organization GO:0042267 natural killer cell mediated cytotoxicity GO:0042269 regulation of natural killer cell mediated cytotoxicity GO:0042271 susceptibility to natural killer cell mediated cytotoxicity GO:0044409 entry into host GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045216 cell-cell junction organization GO:0045954 positive regulation of natural killer cell mediated cytotoxicity GO:0046718 viral entry into host cell GO:0051701 interaction with host GO:0051806 entry into cell of other organism involved in symbiotic interaction GO:0051828 entry into other organism involved in symbiotic interaction GO:0060370 susceptibility to T cell mediated cytotoxicity GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules
Molecular Function	GO:0001618 virus receptor activity GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0005913 cell-cell adherens junction GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04514 Cell adhesion molecules (CAMs)
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-418990: Adherens junctions interactions R-HSA-446728: Cell junction organization R-HSA-1500931: Cell-Cell communication R-HSA-421270: Cell-cell junction organization R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-420597: Nectin/Necl trans heterodimerization

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PVR 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 PVR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25893601	Plasma Cell Myeloma	Promote immunity (T cell function)	In this study using this unique mouse model of multiple myeloma (MM), we demonstrate the importance of NK and CD8+ T cells in MM immunosurveillance and response to treatment in vivo through CD226 and CD155 interactions.
19801517	Ovarian Carcinoma	Promote immunity	Coincubation of NK cells with ovarian carcinoma cells expressing the DNAM-1 ligand CD155 led to reduction of DNAM-1 expression. Therefore, NK cell-mediated rejection of ovarian carcinoma may be limited by perturbed DNAM-1 expression on tumor-associated NK cells induced by chronic ligand exposure.
29308322	Melanoma	Promote immunity (NK cell function)	We demonstrate that BRAFV600E mutant melanoma cells cultured in the presence of vemurafenib, strongly decreased surface expression of ligands for NK activating receptors including the NKG2D-ligand, MICA, and the DNAM-1 ligand, CD155, and became significantly less susceptible to NK cell attack.
29757192	Melanoma; Colon Adenocarcinoma; Fibrosarcoma	Inhibit immunity (T cell function); Resistant to immunotherapy	CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. Cd155-/- mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8+ T and NK cells, respectively. CD155-deleted tumor cells also displayed slower tumor growth and reduced metastases, demonstrating the importance of a tumor-intrinsic role of CD155. CD155 absence on host and tumor cells exerted an even greater inhibition of tumor growth and metastasis. Blockade of PD-1 or both PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of cotargeting PD-L1 and CD155 function.
25209846	Hepatocellular Carcinoma	Promote immunity（NK cell function)	Here, we demonstrated that activated unfolded protein response (UPR) attenuated the sensitivity of human hepatocellular carcinoma cell (HCC) to NK-cell cytotoxicity by decreasing the expression level of CD226 ligand CD155 in HCC
23349395	Hepatocellular Carcinoma	Promote immunity	Here, we show that DNA damage response–induced expression of the DNAM-1 ligand CD155 in tumor cells leads to spontaneous rejection of tumor cells from the blood of young Em-myc mice

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
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 PVR 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	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
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 PVR 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	0.131	0.692
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.173	0.912
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.35	0.775
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.429	0.252
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.676	0.689
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.12	0.957
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.149	0.73
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.34	0.821
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.071	0.965
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.286	0.838
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	0.845	0.669
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.011	0.917

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PVR 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	0	0	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	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	1.4	6	0.177
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	7.4	1.7	5.7	0.231
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	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PVR. 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	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PVR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PVR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PVR. 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	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PVR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PVR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PVR
Name	poliovirus receptor
Aliases	CD155; HVED; Necl-5; NECL5; Tage4; nectin-like 5; PVS; nectin-like protein 5; CD antigen CD155
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PVR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PVR.

ID	Name	Drug Type	Targets	#Targets
DB03203	Sphingosine	Small Molecule	GLTP, PVR	2
DB08231	Myristic acid	Small Molecule	ABL1, ARF1, ARF6, ECI2, FKBP1A, GM2A, GUCA1A, HNF4A, INS, LY96, NC ......	20

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