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Browse IL21

Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
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
 
Subcellular Location Secreted
Domain PF02372 Interleukin 15
Function

Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
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:0002228 natural killer cell mediated immunity
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
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:0002715 regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer cell mediated immunity
GO:0007159 leukocyte cell-cell adhesion
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0021700 developmental maturation
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030888 regulation of B cell proliferation
GO:0030890 positive regulation of B cell proliferation
GO:0031341 regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032609 interferon-gamma production
GO:0032620 interleukin-17 production
GO:0032649 regulation of interferon-gamma production
GO:0032660 regulation of interleukin-17 production
GO:0032729 positive regulation of interferon-gamma production
GO:0032740 positive regulation of interleukin-17 production
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
GO:0042035 regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042095 interferon-gamma biosynthetic process
GO:0042098 T cell proliferation
GO:0042100 B 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:0042113 B cell activation
GO:0042129 regulation of T cell proliferation
GO:0042267 natural killer cell mediated cytotoxicity
GO:0042269 regulation of natural killer cell mediated cytotoxicity
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042508 tyrosine phosphorylation of Stat1 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042510 regulation of tyrosine phosphorylation of Stat1 protein
GO:0042511 positive regulation of tyrosine phosphorylation of Stat1 protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0045072 regulation of interferon-gamma biosynthetic process
GO:0045078 positive regulation of interferon-gamma biosynthetic process
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045785 positive regulation of cell adhesion
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046651 lymphocyte proliferation
GO:0048469 cell maturation
GO:0048771 tissue remodeling
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050863 regulation of T cell activation
GO:0050864 regulation of B cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050871 positive regulation of B 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:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0097696 STAT cascade
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
Molecular Function GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005134 interleukin-2 receptor binding
GO:0070851 growth factor receptor binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04630 Jak-STAT signaling pathway
Reactome -
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IL21 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
 
  Literatures describing the relation between IL21 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26194763Mantle Cell LymphomaPromote immunity (T/NK cell function)Together, these data indicate that IL-21 has potent antitumor activity against MCL cells via direct cytotoxic and indirect, immune-mediated effects.
18413772Melanoma; Renal Cell CarcinomaPromote immunity (T cell function); increase the efficacy of immunotherapyInterleukin 21 enhances antibody-mediated tumor rejection. Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15 that has antitumor activity alone in mouse experimental tumor models and a tolerable safety profile in phase I trials in patients with metastatic melanoma and renal cell carcinoma. Herein, we show that sequentially combining TrimAb with recombinant IL-21 can significantly improve the antitumor activity of this combination against very advanced disease. These data further support the use of IL-21 in adjuvant settings where strong T cell-mediated immune responses to tumors can be generated.
18281483Primary Cutaneous T-Cell Non-Hodgkin LymphomaPromote immunityThey also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T-cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, natural killer, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
18276844Melanoma; Kidney CarcinomaInhibit immunity (T cell function)Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8(+) T-cell phenotype.
16424205Breast AdenocarcinomaPromote immunityCD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. In conclusion, immunotherapy of micrometastases by an IL-21-based cellular vaccine is strongly potentiated by CD25+ cell depletion.
28585539Colorectal Carcinoma; Melanoma; Bladder CarcinomaPromote immunity (T cell function)IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours.
19915059LymphomaInhibit immunity (T cell function)Surprisingly, host IL-21 significantly restricted the expansion of Ag-specific CD8(+) T cells and inhibited primary CD8(+) T cell immunity against OVA-expressing EG7 lymphomas, as well as the secondary expansion of memory CD8(+) T cells.
20039320Stage 4 NeuroblastomaPromote immunity (T cell function); essential for immunotherapyTransient depletion of CD4(+) T cells augments IL-21-based immunotherapy of disseminated neuroblastoma in syngeneic mice. Neuro2a/IL-21 vaccination showed increased expression of IFN-alpha2, -beta1 and -gamma mRNA. In conclusion, anti-CD4 mAb potentiated IL-21-based IT by removing Treg cells and/or their precursors and other potentially immune-suppressive CD4+ cell subsets, thus allowing the development of an IL-21-driven CD8+ T cell response, which mediates NB rejection.
19949105MelanomaPromote immunityAn analysis of different supportive cytokine mixtures during the REP found that a combination of IL-15 and IL-21 facilitated comparable expansion of CD8(+) TILs as IL-2, but prevented the loss of CD28 expression with improved responsiveness to antigenic restimulation post-REP. A REP protocol using IL-15 and IL-21 may greatly increase the number of CD28(+) TILs capable of long-term persistence.
19949105MelanomaPromote immunityAn analysis of different supportive cytokine mixtures during the REP found that a combination of IL-15 and IL-21 facilitated comparable expansion of CD8(+) TILs as IL-2, but prevented the loss of CD28 expression with improved responsiveness to antigenic restimulation post-REP. A REP protocol using IL-15 and IL-21 may greatly increase the number of CD28(+) TILs capable of long-term persistence.
18684866Hodgkin LymphomaInhibit immunity (T cell function)Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3alpha. We demonstrate that IL-21 activates STAT3 in HRS cells, up-regulates STAT3 target genes, and protects HRS cells from CD95 death receptor-induced apoptosis. Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3alpha (MIP-3alpha) in HRS cells.
16081794MelanomaPromote immunityWe demonstrate that exposure to IL-21 increased the total number of MART-1-specific CD8+ T cells that could be elicited by >20-fold and, at the clonal level, enriched for a population of high-affinity CD8+ T cells with a peptide dose requirement more than 1 log(10)-fold less than their untreated counterparts. Our studies demonstrate a significant role for IL-21 in the primary Ag-specific human CTL response and support the use of IL-21 in the ex vivo generation of potent Ag-specific CTLs for adoptive therapy or as an adjuvant cytokine during in vivo immunization against tumor Ags.
16081783Breast Carcinoma; Lung Carcinoma; Prostate CarcinomaPromote immunityIL-21 is a cytokine that can promote the anti-tumor responses of the innate and adaptive immune system. Collectively, these findings suggest that IL-21 therapy may work optimally against tumors that can elicit a NKG2D-mediated immune response.
17582604GliomaPromote immunityMost notably 100% of the animals receiving a primary implant of IL-21-transduced cells rejected the implant, and 76% of these animals survived to a subsequent rechallenge with GL261 parental cells. More importantly, IL-21-secreting GL D2-60 cells or 1 microg of rIL-21 protein stereotactically injected into established GL D2-60 tumors were able to trigger glioblastoma rejection in 90 and 77% of mice, respectively.
25200249melanomaPromote immunityThis is consistent with the observations by us and others that IL-21 alone did not drive a large expansion of CD8+ T cells but synergized with IL-7 or IL-15 to promote CD8+ T cell proliferation while curtailing acquisition of a hypo-proliferative terminally-differentiated phenotype [101,102].
23384943Pan-CancerInhibit immunityOur findings show for the first time that IL-21 induces GrB(+) human Bregs. They also establish the existence of human B cells with a regulatory phenotype in solid tumor infiltrates, where they may contribute to the suppression of antitumor immune responses.
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
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
  Statistical results of IL21 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
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
 
Points in the above scatter plot represent the expression difference of IL21 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)141201
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)6501
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)8701
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-2.2810.0295
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-2.4240.14
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-2.1050.294
729033130MelanomaallAnti-PD-1 (nivolumab) 262301
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 151101
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 111201
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 4801
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 2801
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.7920.000663
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IL21 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.407.40.0709
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.407.40.096
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL21. 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
 
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL21. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL21.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL21. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IL21 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IL21 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIL21
Nameinterleukin 21
Aliases Za11; CVID11; interleukin-21 isoform; Interleukin-21
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IL21 collected from DrugBank database.
> Drugs from DrugBank database
 

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