Browse IL2

Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
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 PF00715 Interleukin 2
Function

Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.

> Gene Ontology
 
Biological Process GO:0000018 regulation of DNA recombination
GO:0001558 regulation of cell growth
GO:0001776 leukocyte homeostasis
GO:0001777 T cell homeostatic proliferation
GO:0001783 B cell apoptotic process
GO:0001819 positive regulation of cytokine production
GO:0001933 negative regulation of protein phosphorylation
GO:0002200 somatic diversification of immune receptors
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response
GO:0002208 somatic diversification of immunoglobulins involved in immune response
GO:0002250 adaptive immune response
GO:0002260 lymphocyte homeostasis
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002377 immunoglobulin production
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus
GO:0002637 regulation of immunoglobulin production
GO:0002639 positive regulation of immunoglobulin production
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002695 negative 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:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
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:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B 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:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0002902 regulation of B cell apoptotic process
GO:0002903 negative regulation of B cell apoptotic process
GO:0003013 circulatory system process
GO:0003015 heart process
GO:0006310 DNA recombination
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0007159 leukocyte cell-cell adhesion
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0008015 blood circulation
GO:0008016 regulation of heart contraction
GO:0009306 protein secretion
GO:0010720 positive regulation of cell development
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0016049 cell growth
GO:0016064 immunoglobulin mediated immune response
GO:0016358 dendrite development
GO:0016444 somatic cell DNA recombination
GO:0016445 somatic diversification of immunoglobulins
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019724 B cell mediated immunity
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030101 natural killer cell activation
GO:0030217 T cell differentiation
GO:0030307 positive regulation of cell growth
GO:0030888 regulation of B cell proliferation
GO:0030890 positive regulation of B cell proliferation
GO:0031346 positive regulation of cell projection organization
GO:0031348 negative regulation of defense response
GO:0031349 positive regulation of defense response
GO:0032102 negative regulation of response to external stimulus
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:0032844 regulation of homeostatic process
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative 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:0038034 signal transduction in absence of ligand
GO:0042098 T cell proliferation
GO:0042100 B cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042104 positive regulation of activated T cell proliferation
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0042129 regulation of T cell proliferation
GO:0042326 negative regulation of phosphorylation
GO:0042506 tyrosine phosphorylation of Stat5 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042522 regulation of tyrosine phosphorylation of Stat5 protein
GO:0042523 positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043029 T cell homeostasis
GO:0044057 regulation of system process
GO:0045066 regulatory T cell differentiation
GO:0045190 isotype switching
GO:0045191 regulation of isotype switching
GO:0045471 response to ethanol
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045589 regulation of regulatory T cell differentiation
GO:0045591 positive regulation of regulatory T cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045822 negative regulation of heart contraction
GO:0045830 positive regulation of isotype switching
GO:0045911 positive regulation of DNA recombination
GO:0045927 positive regulation of growth
GO:0046006 regulation of activated T cell proliferation
GO:0046013 regulation of T cell homeostatic proliferation
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046651 lymphocyte proliferation
GO:0048291 isotype switching to IgG isotypes
GO:0048302 regulation of isotype switching to IgG isotypes
GO:0048304 positive regulation of isotype switching to IgG isotypes
GO:0048305 immunoglobulin secretion
GO:0048771 tissue remodeling
GO:0048872 homeostasis of number of cells
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050727 regulation of inflammatory response
GO:0050728 negative 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:0050769 positive regulation of neurogenesis
GO:0050773 regulation of dendrite development
GO:0050798 activated T cell proliferation
GO:0050863 regulation of T cell activation
GO:0050864 regulation of B cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative 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:0051023 regulation of immunoglobulin secretion
GO:0051024 positive regulation of immunoglobulin secretion
GO:0051047 positive regulation of secretion
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051222 positive regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051962 positive regulation of nervous system development
GO:0055074 calcium ion homeostasis
GO:0060047 heart contraction
GO:0060996 dendritic spine development
GO:0060998 regulation of dendritic spine development
GO:0060999 positive regulation of dendritic spine development
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070229 negative regulation of lymphocyte apoptotic process
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0071887 leukocyte apoptotic process
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097305 response to alcohol
GO:0097696 STAT cascade
GO:1900006 positive regulation of dendrite development
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903522 regulation of blood circulation
GO:1903523 negative regulation of blood circulation
GO:1903532 positive regulation of secretion by cell
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:1904951 positive regulation of establishment of protein localization
GO:2000106 regulation of leukocyte apoptotic process
GO:2000107 negative regulation of leukocyte apoptotic process
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005134 interleukin-2 receptor binding
GO:0008047 enzyme activator activity
GO:0008083 growth factor activity
GO:0019207 kinase regulator activity
GO:0019209 kinase activator activity
GO:0030246 carbohydrate binding
GO:0031628 opioid receptor binding
GO:0031851 kappa-type opioid receptor binding
GO:0043208 glycosphingolipid binding
GO:0046625 sphingolipid binding
GO:0051861 glycolipid binding
GO:0070851 growth factor receptor binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04151 PI3K-Akt signaling pathway
hsa04630 Jak-STAT signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04672 Intestinal immune network for IgA production
Reactome R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-392451: G beta
R-HSA-397795: G-protein beta
R-HSA-388396: GPCR downstream signaling
R-HSA-114604: GPVI-mediated activation cascade
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-109582: Hemostasis
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IL2 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 IL2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26768655Hepatocellular Carcinoma; Cervical CarcinomaPromote immunity (T cell function)A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response. CU-3 competitively reduced the affinity of DGKα for ATP, but not diacylglycerol or phosphatidylserine. Moreover, this compound induced apoptosis in HepG2 hepatocellular carcinoma and HeLa cervical cancer cells while simultaneously enhancing the interleukin-2 production of Jurkat T cells.
26364607Gastric CarcinomaPromote immunity (NK cell function)In contrast, another cell line AGS expressing low levels of HLA-I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression.
26324768Hepatocellular CarcinomaPromote immunity (T cell function)FOXP3/NFAT interaction is required to repress expression of IL-2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function to Tregs.
26141620MelanomaPromote immunity (T cell function)We found that the combination of agonistic anti-CD40 + IL2/anti-IL2 complexes (IL2cx) + IL12Fc was a distinctively effective treatment with respect to priming protective, tumor-specific immunity and eradicating tumors at advanced disease stage.
26019274MelanomaPromote immunity (T cell function)Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth.
25582080Sarcoma; Colon CarcinomaPromote immunityHere, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models.
22704448Renal Cell CarcinomaPromote immunityRadio frequency ablation of the primary tumor combined with interleukin-2 induces a systemic antitumor immune response to renal cell carcinoma, which is much stronger than that of interleukin-2 monotherapy.
22472122Hepatocellular CarcinomaPromote immunityIn an advanced murine metastatic liver tumor model, IL-2 inhibited tumor growth in a dose-dependent fashion. Taken together, our findings provide a novel clinical strategy to enhance the efficacy of HDIL-2 immunotherapy for patients with cancer.
27777574Colorectal carcinomaPromote immunityIL-2 and IL-15 in combination with cetuximab stimulated NK cell, improving cytotoxicity.
27769244Bladder carcinomaPromote immunityNK cells from healthy donors upon activation with IL-2 and IL-15 kills indiscriminately both stem-like and differentiated tumor cells via stress ligand recognition.
24489097LeukemiaPromote immunity (T cell function); increase the efficacy of immunotherapyHuman γδ thymocytes are functionally immature and differentiate into cytotoxic type 1 effector T cells upon IL-2/IL-15 signaling. The effects of IL-2/IL-15 depended on MAPK/ERK signaling and induced de novo expression of the transcription factors T-bet and eomesodermin, as well as the cytolytic enzyme perforin, required for the cytotoxic type 1 program. These findings have implications for the manipulation of γδ T cells in cancer immunotherapy.
18276844Melanoma; Kidney CarcinomaPromote immunity (T cell function); essential for immunotherapyAlthough IL-2 was identified in 1976 and approved for clinical use in 1992, our appreciation of the full range of its actions is still evolving. IL-2 promotes T-cell proliferation, induces tumor-killing lymphocytes, and causes regression of melanoma and kidney cancer in patients.
16434984Metastatic Renal Cell CarcinomaPromote immunity; essential for immunotherapyMonocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). The study provides evidence that circulating monocytes and neutrophils are powerful negative prognostic factors for IL-2-based immunotherapy and establishes a biological rationale for the potential use of histamine in conjunction with IL-2 in mRCC.
16424173Metastatic Renal Cell CarcinomaEssential for immunotherapyCXCR3/CXCR3 ligand biological axis impairs RENCA tumor growth by a mechanism of immunoangiostasis. Metastatic renal cell carcinoma (RCC) responds poorly to chemo- or radiation therapy but appears to respond to systemic immunotherapy (i.e., IL-2 and/or IFN-alpha), albeit with only 5-10% durable response. These data suggest that the combined strategy of systemic IL-2 with intratumor CXCR3 ligand is more efficacious than either strategy alone for reducing tumor-associated angiogenesis and augmenting tumor-associated immunity, the concept of immunoangiostasis.
16424164Breast carcinomaPromote immunity (NK cell function)Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. We propose that tumor exosomes contribute to the growth of tumors by blocking IL-2-mediated activation of NK cells and their cytotoxic response to tumor cells.
27357626MelanomaPromote immunity (T cell function)Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression.
23192659Mesothelioma and lung carcinoma; breast carcinoma; colon carcinoma; gastric carcinoma; bladder carcinoma; uterus carcinomaPromote immunityUpon culture in IL-2, they acquired a potent cytolytic activity against both allogeneic and autologous tumor cells.
19402060Renal cell carcinomaPromote immunityThe most consistent antitumor activity has been reported with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). In recent years, randomized trials have suggested that high-dose, intravenous bolus IL-2 is superior in terms of response rate and possibly in terms of response quality to regimens that involve either low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose IFN-alpha alone.
28497796MelanomaPromote immunity (T cell function)Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region.
28473400Colon CarcinomaPromote immunitycombining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity.
23440412Breast CarcinomaPromote immunity (T cell function)The proportion of MDSCs with the phenotype of CD45(+)CD13(+)CD33(+)CD14(-)CD15(-) significantly increased in primary cancer tissues and patients' peripheral blood. IDO expression was significantly upregulated in MDSCs isolated from fresh breast cancer tissues (fresh MDSCs [fMDSCs]), which correlated with increased infiltration of Foxp3(+) regulatory T cells in tumors and lymph node metastasis in patients. fMDSCs inhibited IL-2 and anti-CD3/CD28 mAb-induced T cell amplification and Th1 polarization but stimulated apoptosis in T cells in an IDO-dependent manner.
23436794MelanomaPromote immunityImmunostimulatory agonists such as anti-CD137 and interleukin (IL)-2 have elicited potent antitumor immune responses in preclinical studies, but their clinical use is limited by inflammatory toxicities that result upon systemic administration. We anchored anti-CD137 and an engineered IL-2Fc fusion protein to the surfaces of PEGylated liposomes, whose physical size permitted dissemination in the tumor parenchyma and tumor-draining lymph nodes but blocked entry into the systemic circulation following intratumoral injection. In the B16F10 melanoma model, intratumoral liposome-coupled anti-CD137 + IL-2Fc therapy cured a majority of established primary tumors while avoiding the lethal inflammatory toxicities caused by equivalent intratumoral doses of soluble immunotherapy.
21282337Breast Carcinoma; Lung CarcinomaPromote immunityAnti-IL-23 monoclonal antibody synergizes in combination with targeted therapies or IL-2 to suppress tumor growth and metastases. More notably, combinatorial treatments of anti-IL-23 mAb with IL-2 or anti-erbB2 mAb significantly inhibited subcutaneous growth of established mammary carcinomas and suppressed established experimental and spontaneous lung metastases. Overall, our results suggest the potential of anti-human IL-23 mAbs to improve the immunostimulatory effects of IL-2 and trastuzumab in the current management of some advanced human cancers.
21224372MelanomaPromote immunity (T cell function)A dynamic label free assay was used to determine the pathways involved in the lysis of melanoma cells by IL-2-activated NK cells. NKG2D, NCR (natural cytotoxicity receptor), and DNAM-1 are involved in the NK-mediated lysis of melanoma cells.
21165950Leukemia; MelanomaPromote immunity (T cell function)Here, we show that IL-2/S4B6 mAb immunocomplexes expand not only CD122(high) subsets and newly activated CD8(+) T cells but also natural killer T cells and γδ T cells. Further, we demonstrate that natural killer (NK) cells expanded by IL-2/S4B6 mAb immunocomplexes in vivo have high cytolytic activity, which can be further increased by coadministration of IL-12. We also demonstrate that IL-2/S4B6 mAb immunocomplexes possess noticeable antitumor activity in two syngeneic mouse tumor models, namely BCL1 leukemia and B16F10 melanoma, but only if administered early in tumor progression. To effectively treat established tumors, we administered the tumor-bearing mice first with N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate, and subsequently with IL-2/S4B6 mAb immunocomplexes alone or with IL-12 to induce an efficient antitumor immune response.
16785526MelanomaPromote immunity (T cell function)Here we show that a widely used neutralizing anti-murine IL-2 mAb (S4B6) exhibits unexpected activities that enhance the treatment effects of IL-2 in vivo. A 5-day treatment with the anti-IL-2 mAb alone gradually increased the CD44(high)CD8+ population, and the increased population was maintained for >300 days, suggesting that the mAb can gradually maintain and potentially enhance the bioactivity of endogenous IL-2 for extended periods. 16785526-7 IL2 IL-2 These results demonstrated IL-2-enhancing effects of the anti-IL-2 mAb in vivo and suggest that combining a neutralizing anti-IL-2 Ab with IL-2 gene delivery might be used effectively to enhance IL-2 functions in clinical applications.
16751420MelanomaPromote immunity (T cell function)Incubation in vitro with high doses of IL-2 (3,000 IU/ml) or administration of IL-2 in vivo resulted in substantial up-regulation of CD70 expression and the concomitant loss of cell surface CD27 expression on CD8(+) cells. Withdrawal of IL-2 from activated CD8(+) T cells that had been maintained in IL-2 resulted in a reversal of the expression of these two markers, whereas reciprocal changes were seen following treatment of PBMCs with IL-2. The proliferation observed in cells stimulated with IL-2 primarily occurred in a subset of the CD70(+)CD8(+) T cells that up-regulated IL-2 receptor expression but did not occur in CD70(-)CD8(+) T cells. Blocking CD70 resulted in a significant reduction of T cell proliferation induced by high-dose IL-2, indicating that the interaction of CD70 with CD27 played a direct role in T cell activation mediated by IL-2. Finally, studies conducted on tumor-infiltrating lymphocyte (TIL) samples that were administered to melanoma patients indicated that the size of the pool of CD27(+)CD8(+) T cells in bulk TILs was highly associated (p = 0.004) with the ability of these TILs to mediate tumor regression following adoptive transfer.
16621991MelanomaInhibit immunity (T cell function)IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance in vivo. IL-2 is mainly produced by CD4(+) Th cells, but the role of Th cell-derived IL-2 in vivo is controversial. We demonstrate that during immunity to a tumor/self-Ag, the predominant role of Th cell-derived IL-2 was to maintain IL-2Ralpha (CD25) on CD4(+) T regulatory cells (T(reg)), which resulted in their maintenance of the T(reg) cell lineage factor, Forkhead/winged helix transcription factor (Foxp3), and tolerance. Lastly, administration of anti-IL-2 plus exogenous IL-15 to tumor-bearing mice enhanced the adoptive immunotherapy of cancer.
23770212HER2 Positive Breast CarcinomaPromote immunity (T cell function); essential for immunotherapyAn antibody-cytokine fusion protein consisting of the immunostimulatory cytokine interleukin-2 (IL-2) genetically fused to an antibody specific for human HER2/neu [anti-HER2/neu IgG3-(IL-2)] was covalently attached to the PMLA backbone to target HER2/neu expressing tumors and ensure the delivery of IL-2 to the tumor microenvironment. The nanobioconjugate exhibited marked anti-tumor activity manifested by significantly longer animal survival and significantly increased anti-HER2/neu immune response in immunocompetent mice bearing D2F2/E2 murine mammary tumors that express human HER2/neu.
23677467Melanoma; Lung CarcinomaPromote immunity (T cell function)The IL-2 mutant induces in vitro proliferation of CD8(+)CD44(hi) and NK1.1 cells as efficiently as does wtIL-2, but it shows a reduced capacity to induce proliferation of CD4(+)Foxp3(+) regulatory T cells. The IL-2 mutant shows a higher antimetastatic effect than does wtIL-2 in several transplantable tumor models: the experimental metastasis model of MB16F0 melanoma and the experimental and spontaneous metastasis models for the mouse pulmonary carcinoma 3LL-D1222.
22419581MyelomaPromote immunity (NK cell function)Expanded natural killer cells killed both allogeneic and autologous primary myeloma cells avidly via a perforin-mediated mechanism in which the activating receptor NKG2D, natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central role. The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis.
22374980Prostate CarcinomaInhibit immunity (T cell function)In addition, Treg expansion in Pten(-/-) mice was prevented by in vivo interleukin (IL)-2 blockade suggesting that increased IL-2 generated by castration and immunization promotes Treg expansion.
18056198Ovarian CarcinomaPromote immunity (T cell function); essential for immunotherapyCD8+ T cells induce complete regression of advanced ovarian cancers by an interleukin (IL)-2/IL-15 dependent mechanism.
17332365NeuroblastomaPromote immunity (T/NK cell function)Therefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2-enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines.
17332301Lung CarcinomaPromote immunity (NK cell function)A logarithmic correlation was observed between the number of EGFRs and ADCC activity. In addition, ADCC activity was enhanced by interleukin-2 mainly through activation of NK cells and was less susceptible to immunosuppression by chemotherapy than NK activity in lung cancer patients.
24778448MelanomaPromote immunityNaive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2-dependent manner into IFN-γ-producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8(+) T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2-producing cells to differentiate into IFN-γ-producing effectors.
20940398Pancreatic CarcinomaPromote immunityProduction of interleukin-2 by tumor resident CD4(+) T cells enhanced CD8(+) T-cell proliferation and upregulated expression of granzyme B.
19880164Ovarian CarcinomaPromote immunity (NK cell function)Therapy consisted of low-dose subcutaneous IL-2 and oral RA, administered on intermittent schedules for up to 5 years. A statistically significant improvement in lymphocyte and NK counts and a decrease in VEGF levels were observed with respect to baseline values among the 65 evaluable patients.
19201693Renal Cell CarcinomaInhibit immunity (T cell function)High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I
19188179Renal Cell CarcinomaInhibit immunityIncreased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma. A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing baseline (median 23 cells/mm2; range, 0-183) and on-treatment biopsies (median, 89 cells/mm2; range, 11-388; P < 0.001). FOXP3-positive cells were positively correlated with CD3-positive, CD4-positive, and CD8-positive tumor-infiltrating immune cells at baseline and during treatment (P < 0.05 in all comparisons). All patients achieving high numbers (>180 cells/mm2) of on-treatment FOXP3-positive intratumoral immune cells were dead within 22 months (n = 11), whereas patients with low numbers (<180 cells/mm2) of on-treatment FOXP3-positive cells (n = 31) had a 5-year survival rate of 19% (hazard ratio, 2.2; confidence interval, 1.03-4.5; P = 0.043).
25024217melanomaPromote immunity (T cell function); essential for immunotherapyA20-deleted CD8 T cells had increased sensitivity to antigen stimulation with production of large amounts of IL-2 and IFNγ, correlated with sustained nuclear expression of NF-κB components reticuloendotheliosis oncogene c-Rel and p65.
25000978Stage IV Squamous Cell Lung Carcinoma AJCC v7Promote immunity (T&NK cell function)Because of increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL-2 with Abs to neutralize TGF-β, a potent immunosuppressive cytokine, was assessed.
24907378melanoma and Kidney CarcinomaPromote immunity (infiltration)The growth of large numbers of tumor-infiltrating lymphocytes with in vitro anti-cancer activity in IL-2 has led to the development of cell transfer therapies that are highly effective in patients with melanoma.
29683892Esophageal squamous cell carcinomaPromote immunity (NK cell function); essential for immunotherapyThe cytotoxicity of resting and of IL-2-activated NK cells against ESCC cell lines was compared with that of expanded NK cells.
29664568melanomaPromote immunity (T cell function); increase the efficacy of immunotherapyDuring immune responses, augmented levels of IL-2, IL-15, IL-21, IL-12, IL-18, and type-I interferons determine the memory potential of antigen-specific effector CD8+ cells, while increased IL-2 and IL-15 cause bystander proliferation of heterologous CD4+ and CD8+ memory T cells.
29618524melanomaInhibit immunity (T cell function)Our results show that it is enough to transiently inhibit IL-2 signaling to bias E and Treg cell balance in vivo toward immunity.
29616326Lung Carcinoma; Non-small cell lung carcinoma; Small cell lung carcinomaPromote immunity (Nk cell function); increase the efficacy of immunotherapyRecent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival.
29577276Plasma Cell MyelomaPromote immunity (T function); essential for immunotherapyThis is due to the modulation of IL-2 and IL-15 signaling, which is required for expansion and survival of CD8+ T cells as well as for optimal cytotoxic activity.
27742794Renal Cell CarcinomaPromote immunityFCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma. We hypothesize that endogenous antitumor antibodies may engage immune cells through their FCGRs, and HD-IL2 may enhance antibody-induced tumor destruction, or antibody-enhanced tumor antigen presentation, via augmented activation of innate or adaptive immune responses.
23871358Acute Myeloid LeukemiaPromote immunityWe envisage future treatment protocols, in which systemic immune activators, such as vaccines, dendritic cell-based therapies, engineered variants of IL-2, or IL-15, are combined with agents that counter immunosuppression mediated by, e.g., the PD/PDL interaction, CTLA-4, CD200, reactive oxygen species, IDO expression, CXCR4, or the KIR/class I interaction, based on characteristics of the prevailing malignant clone.
21540460Chronic Lymphocytic LeukemiaPromote immunity (T cell function)Donor-derived mature dendritic cells generated in vitro from CD14(+) monocytes were loaded with human leukocyte Ag-restricted peptides derived from PR1, WT1, and/or B-cell receptor-ABL and used to repetitively stimulate donor CD8(+) T cells in the presence of IL-2 and IL-7.
21531812Non-Small Cell Lung Carcinoma; NeuroblastmaPromote immunityThe goal of the study was to engineer a form of interleukin 2 (IL-2) that, when delivered as a tumor-specific antibody fusion protein, retains the ability to stimulate an antitumor immune response via interaction with the high-affinity IL-2 receptor but has lower toxicity because of the reduced activation of the intermediate-affinity IL-2 receptor.
21518728B16 Malignant MelanomaPromote immunity (T cell function)Furthermore, we showed that H1/pIL-2 stimulated the activation and proliferation of CD8+, CD4+ T cell, and natural killer cells in peripheral blood and increased the infiltration of CD8+, CD4+ Tcells, and natural killer cells into the tumor environment.
21453957Ovarian CancinomaPromote immunityHuman serum did not significantly inhibit hRS7-mediated cytotoxicity while incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity (p=0.04).
21406718Chronic Lymphocytic LeukemiaPromote immunityIL-2 was also produced (average release 2681 pg/mL) and sustained the antigen-dependent proliferation of CD23.CAR(+) T cells.
21355077MelanomaPromote immunity (T cell function)IL2 and IL15 can be synergistic in moDC stimulation of cytolytic T cells.
21325070MelanomaIncrease the efficacy of immunotherapyA number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival.
20072155B-cell Chronic Lymphocytic LeukemiaPromote immunityWe examined the fate of these cells in six of these individuals who received autologous human CD40 ligand and interleukin-2 (hCD40L/IL-2) gene-modified tumor cells as part of a tumor vaccine study. Vaccinated patients showed an increase in B-CLL-reactive T cells followed by a corresponding decline in circulating CD5(+)CD19(+) SP cells.
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. These results suggest that current expansion protocols using IL-2 for melanoma adoptive T cell therapy yields largely CD8(+) T cells unable to persist and divide in vivo following Ag contact.
19934056MelanomaPromote immunity (NK cell function)Thus, both the IL-2-induced up-regulation of the surface expression of NKp44, NKp30, and DNAM-1 triggering receptors and the acquisition of cytolytic granules were inhibited in NK cells. This resulted in an impairment of the NK cell-mediated killing of melanoma target cells.
29327244MyelomaPromote immunityAntibody-based delivery of tumor necrosis factor (L19-TNFα) and interleukin-2 (L19-IL2) to tumor-associated blood vessels has potent immunological and anticancer activity in the syngeneic J558L BALB/c myeloma model. IL2, TNFα, or IL2 plus TNFα (final 20 h) increased the proportion of CD4- CD25low effector lymphocytes possibly indicating immune activation.
29327110NeuroblastomaPromote immunityVarious strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy. In conclusion, IL-2 is an important component of immunotherapy because it can improve the cytolytic function of NK cells against neuroblastoma cells and could lower the antibody dose required for efficacy, thereby reducing toxicity.
29293164Colorectal CancinomaPromote immunity (NK cell function)Resting NK cells were unable to display sizeable levels of cytotoxic activity against mCRC cells, whereas their cytotoxic activity was enhanced after overnight or 5-day incubation with IL-2 or IL-15.
16061910Colorectal CarcinomaPromote immunityChemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients.
16061683MelanomaPromote immunityHuman high molecular weight melanoma-associated antigen mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: enhancement of immunogenicity of anti-idiotypic monoclonal antibody MK2-23 by fusion with interleukin 2. Conjugation of human interleukin 2 (IL-2) to mAb MK2-23 variable regions covalently linked to human immunoglobulin constant regions enhanced mAb MK2-23 immunogenicity in BALB/c mice to an extent similar to that induced by mAb MK2-23 conjugated to KLH and given with Freund's adjuvant.
15951291Acute Lymphoblastic LeukemiaPromote immunity (NK cell function)In addition, incubating these effectors for 24 hours with IL-2 + IL-15 significantly increased this cytotoxic function.
29187357Lung MelanomaPromote immunityConsistent with this, mature mouse primary iNKT cells and iNKT hybridomas increased production of effector cytokines in the presence of IAP antagonists. In vivo administration of IAP antagonists and α-GalCer resulted in increased IFNγ and IL-2 production from iNKT cells and decreased tumor burden in a mouse model of melanoma lung metastasis.
24292706MelanomaInhibit immunityIL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients. High-dose (HD) IL-2 therapy in patients with cancer increases the general population of Tregs, which are positive for CD4, CD25, and the Treg-specific marker Foxp3.
22972922Colon CarcinomaInhibit immunityMoreover, the administration of IL-2 into tumor-bearing MIF(-/-) mice restored the generation of Tregs and tumor growth.
22932225MelanomaPromote immunityMelanoma-specific T cells screened for high relative IL-2 production had a T(CM) phenotype and superior in vitro proliferative capacity compared to cells with low IL-2 production.
21631324MelanomaPromote immunityIn a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone.
20473905Pancreatic Ductal AdenocarcinomaPromote immunityWe demonstrate here that IL-2-activated human NK cells are able to kill PDAC cells.
29721366MelanomaPromote immunity; Essential for immunotherapyTNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells.
17671219Ovarian CarcinomaInhibit immunityWe show that administration of IL-2 induces the proliferation of existent Treg cells in patients with ovarian cancer. Furthermore, IL-2 treatment stimulates chemokine receptor CXCR4 expression on Treg cells, enables Treg cell migration toward chemokine CXCL12 in the tumor microenvironment, and may enforce Treg cell tumor accumulation.
17595664NeuroblastomaPromote immunityWe conclude that syngeneic fibroblasts cotransfected with IL-2 and IL-12 mediate therapeutic effects against established disease, and are capable of generating immunological memory.
16249392Acute LeukemiaPromote immunityTen patients (including 7 children) with high-risk acute myeloid (n = 4) or lymphoblastic (n = 6) leukemia in cytologic remission (after allogeneic stem cell transplantation [n = 9] or chemotherapy alone [n = 1]) received up to 6 subcutaneous injections of the IL-2/CD40L vaccine. Immunization produced a 10- to 890-fold increase in the frequencies of major histocompatibility complex (MHC)-restricted T cells reactive against recipient-derived blasts.
16203783Chronic Lymphocytic LeukemiaPromote immunityCD40 ligand activates the malignant B-cell chronic lymphocytic leukemia cells and enhances their capacity to present tumor antigens. Human interleukin-2 further potentiates the immunogenicity of human CD40 ligand in preclinical murine models. These results suggest that immune responses to B-cell chronic lymphocytic leukemia can be obtained with human CD40 ligand/human interleukin-2-expressing s.c. vaccines but that these responses are transient.
25200249melanoma; renal cell carcinomaPromote immunityThe infusion of IL-2 at low or high doses for multiple cycles in patients with metastatic melanoma and renal cell carcinoma was the first successful immunotherapy for cancer proving that the immune system could completely eradicate tumor cells under certain conditions.
23296706colon carcinomaPromote immunityMechanistically, poly-G ODN directly induced the phosphorylation of Lck (an essential element of the T cell-signaling pathway), thereby enhancing the production of IL-2 and CD8 T cell proliferation
23281444Colon adenocarcinomaInhibit immunityHere, it was initially verified that cytokine (interleukin (IL)2) or chemokine (CCL5) expression from a systemically delivered oncolytic virus resulted in reduced oncolytic activity and suboptimal immune activation, while IL2 also resulted in increased toxicity
23209317lymphomaPromote immunityIL-12/15/18-preactivated NK cells expressed high levels of IL-2Ralpha (CD25), and their rapid in vivo proliferation depended on IL-2 produced by CD4+ T cells. IL-12/15/18-preactivated NK cells accumulated in the tumor tissue and persisted at high cell numbers with potent effector function that required the presence of CD4+ T cells.
21971567NeuroblastomaPromote immunityThus, the one proven beneficial immunotherapy for patients with high-risk neuroblastoma uses a chimeric anti-GD2 mAb combined with IL-2 and GM-CSF to treat patients after they have received intensive cyto-reductive chemotherapy, irradiation, and surgery
21844012MelanomaPromote immunityHowever, the persistent NK cells in the circulation expressed significantly lower levels of the key activating receptor NKG2D and could not lyse tumor cell targets in vitro unless reactivated with IL-2.
21796616MelanomaPromote immunityThe production of multiple cytokines (IFNgamma, TNFalpha, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
21784871Breast CarcinomaPromote immunityFurthermore, we showed that treatment with these NPs resulted in priming of the immune TME, characterized by increased IFN-gamma, p-STAT-1, GM-CSF, IL-2, IL-15, and IL-12b and reduced TGF-beta, IL-6, and IL-10 protein expression. In addition, we found significantly increased tumor infiltration by activated CD8(+) T cells, M1 macrophages, and dendritic cells.
21782419pancreatic carcinomaPromote immunityPSCs that overexpressed Galectin-1 induced apoptosis of CD4(+) T cells (p < 0.01) and CD8(+) T cells (p < 0.05) significantly, compared to normal PSCs. Knockdown of Galectin-1 in PSCs increased CD4(+) T cell (p < 0.01) and CD8(+) T cell viability (p < 0.05). Supernatants from T cells cocultured with PSCs that overexpressed Galectin-1 contained significantly increased levels of Th2 cytokines (IL-4 and IL-5, p < 0.01) and decreased Th1 cytokines (IL-2 and INF-gamma, p < 0.01).
16990769leukemiaPromote immunityAfter 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10.
16982932lymphomaPromote immunityA single stimulation of CD8+ T cells from healthy virus carriers, and patients with HL with this adenoviral construct in combination with IL-2, was sufficient to reverse the functional T cell impairment and restored both IFN-gamma production and cytolytic function.
16982889mastocytomaPromote immunityHowever, these cells showed poor IFN-gamma and IL-2 production upon restimulation, consistent with T cell anergy and similar to the hyporesponsiveness induced by administration of soluble peptide Ag.
16982775Renal cell carcinomaInhibit immunityDuring the IL-2 treatment, the ATRA effect was completely eliminated. To assess the role of IL-2, specimens from 15 patients with metastatic renal cell carcinoma who had been treated with i.v. IL-2 alone were analyzed. In this group also, IL-2 significantly reduced the number and function of dendritic cells as well as T-cell function.
16968820MelanomaPromote immunityWe examined HMGB1 release from tumor cells following coincubation with NK cells with enhanced lymphokine-activated killing (LAK) activity, induced by IL-2 exposure or mediated by melanoma-specific CTL
16899610melanoma; renal cell carcinomaPromote immunityDecitabine augmented hemoglobin F levels and altered DNA methylation and gene expression in peripheral blood mononuclear cells in a dose-independent manner that overlapped with the administration of IL-2. Objective responses occurred in 31% of melanoma patients. CONCLUSIONS: Decitabine can be safely administered with high-dose IL-2 and may enhance the activity of IL-2 in melanoma.
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
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 IL2 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
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
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 IL2 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) 916-0.7060.482
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.370.798
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-1.1490.538
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) 480.3560.438
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7110.287
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0780.735
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IL2 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) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
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
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
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 IL2. 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
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
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 IL2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IL2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IL2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIL2
Nameinterleukin 2
Aliases IL-2; TCGF; T cell growth factor; lymphokine; aldesleukin; involved in regulation of T-cell clonal expansion ......
Chromosomal Location4q26-q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IL2 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting IL2.
ID Name Drug Type Targets #Targets
DB00852PseudoephedrineSmall MoleculeADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......20
DB01327CefazolinSmall MoleculeIL15, IL2, PON13
DB02555SP4160Small MoleculeIL21
DB025815-[2,3-Dichloro-4-(5-{1-[2-(2-Guanidino-4-Methyl-Pentanoylamino)-Acetyl]-Piperidin-4-Yl}-1-Methyl-1h-Pyrazol-3-Yl)-Phenoxymethyl]-Furan-2-Carboxylic AcidSmall MoleculeIL21
DB033723-Mercapto-1-(1,3,4,9-Tetrahydro-B-Carbolin-2-Yl)-Propan-1-OneSmall MoleculeIL21
DB03453(R)—N[2-[1-(aminoiminomethyl)-3-piperidinyl]-1-oxoethyl]-4-(phenylethynyl)-l-phenylalanine methylesterSmall MoleculeIL21
DB03455(1H-indol-3-yl)-(2-mercapto-ethoxyimino)-acetic acidSmall MoleculeIL21
DB03957SP2456Small MoleculeIL21
DB042782-[2-(2-Cyclohexyl-2-Guanidino-Acetylamino)-Acetylamino]-N-(3-Mercapto-Propyl)-PropionamideSmall MoleculeIL21
DB05299keyhole limpet hemocyaninBiotechIL21
DB05304WX-G250Small MoleculeCA9, IL22
DB05676ApremilastSmall MoleculeIFNG, IL2, NOS3, PDE4A, PDE4B, PDE4D, TNF7
DB06083TapinarofSmall MoleculeCXCL8, IL12B, IL2, IL64