TISIDB

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
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 1: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 2: Secreted
Domain	PF15910 ICOS V-set domain
Function	Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0002507 tolerance induction GO:0002517 T cell tolerance induction GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0007159 leukocyte cell-cell adhesion GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0031294 lymphocyte costimulation GO:0031295 T cell costimulation GO:0042110 T cell activation GO:0045785 positive regulation of cell adhesion GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion
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) hsa04660 T cell receptor signaling pathway hsa04672 Intestinal immune network for IgA production
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-388841: Costimulation by the CD28 family R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-186763: Downstream signal transduction R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-180292: GAB1 signalosome R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-199418: Negative regulation of the PI3K/AKT network R-HSA-2219528: PI3K/AKT Signaling in Cancer R-HSA-198203: PI3K/AKT activation R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1257604: PIP3 activates AKT signaling R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-166520: Signalling by NGF

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04514 Cell adhesion molecules (CAMs)
hsa04660 T cell receptor signaling pathway
hsa04672 Intestinal immune network for IgA production

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-388841: Costimulation by the CD28 family
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ICOS 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

[ TOP ]

Literatures describing the relation between ICOS and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27246829	Follicular Lymphoma	Inhibit immunity (T cell function)	These Tregs comprised activated ICOS(+) Tregs that were able to suppress not only conventional T cells, but also FL B cells.
20980695	Pleural Malignant Mesothelioma	Promote immunity (T cell function)	COS stimulation induced c-MAF, RORC2, and T-bet expression in these cells, leading to increased secretion of interleukin-21 (IL-21), IL-17, and interferon-γ (IFN-γ) compared with cells stimulated with CD28. Conversely, CD28 ligation abrogated ICOS costimulation, dampening RORC2 expression while promoting the expression of the aryl hydrocarbon receptor, which led to reduced secretion of IL-17 and enhanced production of IL-22 compared with cells stimulated with ICOS. Moreover, ICOS promoted the robust expansion of IL-17(+)IFN-γ(+) human T cells, and the antitumor activity of these cells after adoptive transfer into mice bearing large human tumors was superior to that of cells expanded with CD28.
29661826	melanoma	Promote immunity (T cell function); essential for immunotherapy	We find that calcineurin, although largely dispensable for suppressive activity in vitro, is essential for upregulation of ICOS and CTLA-4 in Treg, as well as for expression of chemokine receptors driving their accumulation in tumors.
29614981	Colorectal cancer	Promote immunity (T function); essential for immunotherapy	Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor.

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
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

[ TOP ]

Statistical results of ICOS 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	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
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

[ TOP ]

Points in the above scatter plot represent the expression difference of ICOS 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	0.076	0.853
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.114	0.88
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.221	0.707
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.403	0.627
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.838	0.128
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.41	0.31
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.381	0.0798
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.819	0.115
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.945	0.441
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.321	0.0835
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	1.059	0.32
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0	0.998

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of ICOS 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	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	11.8	-11.8	0.193
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	18.2	-18.2	0.199
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
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	25	0	25	0.364
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	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ICOS. 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	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ICOS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ICOS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ICOS. 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	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ICOS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ICOS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ICOS
Name	inducible T-cell co-stimulator
Aliases	AILIM; CD278; activation-inducible lymphocyte immunomediatory molecule; CVID1; inducible costimulator; CD an ......
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ICOS collected from DrugBank database.

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

Browse ICOS