TISIDB

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
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
Domain	PF07686 Immunoglobulin V-set domain
Function	Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells.

> Gene Ontology [ TOP ]
Biological Process	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:0007156 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0007159 leukocyte cell-cell adhesion GO:0007162 negative regulation of cell adhesion GO:0008037 cell recognition GO:0022407 regulation of cell-cell adhesion GO:0022408 negative regulation of cell-cell adhesion GO:0032613 interleukin-10 production GO:0032615 interleukin-12 production GO:0032653 regulation of interleukin-10 production GO:0032655 regulation of interleukin-12 production GO:0032695 negative regulation of interleukin-12 production GO:0032733 positive regulation of interleukin-10 production GO:0042110 T cell activation GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050868 negative regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051250 negative regulation of lymphocyte activation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903038 negative regulation of leukocyte cell-cell adhesion
Molecular Function	GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0005913 cell-cell adherens junction

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

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TIGIT 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 TIGIT and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26763253	Acute Myeloid Leukemia	Inhibit immunity (T cell function)	TIGIT contributes to functional T-cell impairment and associates with poor clinical outcome in AML.
25680274	Colorectal Carcinoma	Inhibit immunity (NK cell function)	We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2.
23536636	Melanoma	Inhibit immunity (T cell function); essential for immunotherapy	Concomitantly, tumor-specific CD4(+) T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression.
29217528	Follicular Lymphoma	Inhibit immunity	CD8 FL T cells demonstrated highly reduced TCR-induced phosphorylation (p) of ERK and reduced production of IFNγ, while TCR proximal signaling (p-CD3ζ, p-SLP76) was not affected. Dysfunctional TCR signaling correlated with TIGIT expression in FL CD8 T cells and could be fully restored upon in vitro culture.

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
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 TIGIT 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	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
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 TIGIT 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	-0.144	0.801
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.06	0.957
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.297	0.752
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.06	0.847
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.288	0.775
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.226	0.856
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.817	0.025
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	2.705	0.0336
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.914	0.502
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.172	0.228
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	0.837	0.559
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.059	0.805

> Mutation difference between responders and non-responders

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

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	11.1	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TIGIT. 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	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TIGIT. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TIGIT. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TIGIT. 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	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TIGIT expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TIGIT and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TIGIT
Name	T cell immunoreceptor with Ig and ITIM domains
Aliases	FLJ39873; DKFZp667A205; VSIG9; VSTM3; V-set and immunoglobulin domain containing 9; V-set and transmembrane ......
Chromosomal Location	3q13.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TIGIT collected from DrugBank database.

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

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