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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ICOSLG
inducible T cell costimulator ligand
Chromosome 21 · 21q22.3
NCBI Gene: 23308Ensembl: ENSG00000160223.18HGNC: HGNC:17087UniProt: A0A2R8Y5W7
87PubMed Papers
21Diseases
1Drugs
2Pathogenic Variants
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
receptor ligand activityplasma membraneprotein bindingT follicular helper cell differentiationimmunodeficiency 119combined immunodeficiencygenetic disorderCombined T and B cell immunodeficiency
✦AI Summary

ICOSLG (inducible T cell costimulator ligand) is a B7 family costimulatory molecule that primarily functions as a ligand for the T-cell receptor ICOS, enhancing T cell proliferation and cytokine secretion 12. Beyond T cells, ICOSLG induces B cell differentiation into plasma cells [UniProt] and is required for proper neutrophil transmigration in endothelial cells 3. Mechanistically, ICOSLG amplifies pattern-recognition receptor signaling through homotypic ICOS-ICOSL interactions on dendritic cells, recruiting adaptor proteins and activating PKC, MAPK, and NF-κB pathways 4. ICOSLG is critical for mucocutaneous immunity; ICOSLG deficiency causes combined immunodeficiency with recurrent respiratory infections and DNA virus susceptibility at epithelial barriers 5. In cancer contexts, ICOSLG shows bidirectional roles: mesenchymal glioblastoma cells express ICOSLG to expand immunosuppressive IL-10-producing T cells, promoting tumor progression 6, while chemotherapy-induced ICOSL+ B cells enhance anti-tumor immunity by favoring effector T cells 7. High ICOSLG expression correlates with improved response to anti-PD-1 immunotherapy with antihistamine premedication in melanoma 8 and is associated with poor prognosis in gastric cancer through enhanced glycolysis 9. These contrasting roles suggest ICOSLG's function is context- and cell-type dependent.

Sources cited
1
ICOSLG acts as a costimulatory ligand for T-cell proliferation and cytokine secretion
PMID: 11007762
2
ICOSLG functions as a costimulatory signal for T-cell proliferation and cytokine secretion
PMID: 11023515
3
ICOSLG induces B-cell proliferation and is required for neutrophil transmigration in endothelial cells
PMID: 30498080
4
ICOSLG deficiency causes combined immunodeficiency with recurrent respiratory infections and DNA virus disease at epithelial barriers
PMID: 33756276
5
ICOSLG amplifies pattern-recognition receptor signaling through ICOS-ICOSL interactions via RACK1, PKC, and JNK recruitment
PMID: 24837102
6
ICOSLG expressed by mesenchymal glioblastoma cells promotes expansion of IL-10-producing T cells and tumor progression
PMID: 31634400
7
Chemotherapy-induced ICOSL+ B cells enhance anti-tumor immunity by increasing effector to regulatory T cell ratio
PMID: 32142650
8
High ICOSLG expression correlates with better response to anti-PD-1 immunotherapy with antihistamine premedication in melanoma
PMID: 39596506
9
ICOSLG is highly expressed in gastric cancer and promotes glycolysis, proliferation, and migration; high expression associates with poor prognosis
PMID: 38081339
10
ICOSLG is part of an immune glioma survival signature and correlates with immunotherapy resistance in glioma
PMID: 40714831
Disease Associationsⓘ21
immunodeficiency 119Open Targets
0.34Weak
combined immunodeficiencyOpen Targets
0.31Weak
Combined T and B cell immunodeficiencyOpen Targets
0.27Weak
genetic disorderOpen Targets
0.27Weak
rheumatoid arthritisOpen Targets
0.25Weak
depressive disorderOpen Targets
0.16Weak
cardiomyopathyOpen Targets
0.13Weak
benign urinary system neoplasmOpen Targets
0.13Weak
neoplasmOpen Targets
0.12Weak
systemic lupus erythematosusOpen Targets
0.11Weak
type 1 diabetes mellitusOpen Targets
0.10Weak
Sjogren syndromeOpen Targets
0.09Suggestive
infectionOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
BENTA diseaseOpen Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.07Suggestive
Immunodeficiency 119UniProt
Pathogenic Variants2
NM_015259.6(ICOSLG):c.499C>T (p.Pro167Ser)Likely pathogenic
Combined immunodeficiency
★☆☆☆2021→ Residue 167
NM_015259.6(ICOSLG):c.55+1G>TLikely pathogenic
Inborn genetic diseases
★☆☆☆2017
View on ClinVar ↗
Drug Targets1
AMG-557Phase II
ICOS ligand inhibitor
systemic lupus erythematosus
Related Genes
PDCD1LG2Protein interaction99%CD8AProtein interaction97%TNFSF13BProtein interaction96%IL10Protein interaction96%CD80Protein interaction90%TNFSF4Protein interaction87%
Tissue Expression6 tissues
Brain
100%
Lung
42%
Liver
33%
Bone Marrow
12%
Ovary
7%
Heart
4%
Gene Interaction Network
Click a node to explore
ICOSLGPDCD1LG2CD8ATNFSF13BIL10CD80TNFSF4
PROTEIN STRUCTURE
Preparing viewer…
PDB6X4T · 3.15 Å · X-ray
View on RCSB ↗
RankingsWhere ICOSLG stands among ~20K protein-coding genes
  • #5,488of 20,598
    Most Researched87
  • #4,342of 5,498
    Most Pathogenic Variants2
Genes detectedICOSLG
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity.
PMID: 32142650
Cell · 2020
1.00
2
ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma.
PMID: 39596506
Int J Mol Sci · 2024
0.90
3
ICOSL in host defense at epithelial barriers: lessons from ICOSLG deficiency.
PMID: 33756276
Curr Opin Immunol · 2021
0.80
4
Autoimmune muscular pathologies.
PMID: 15883700
Neurol Sci · 2005
0.70
5
ICOSLG-mediated regulatory T-cell expansion and IL-10 production promote progression of glioblastoma.
PMID: 31634400
Neuro Oncol · 2020
0.60