Browse IL12A

Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
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 PF03039 Interleukin-12 alpha subunit
Function

Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated Killer cells, and stimulate the production of IFN-gamma by resting PBMC.

> Gene Ontology
 
Biological Process GO:0001562 response to protozoan
GO:0001818 negative regulation of cytokine production
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:0001913 T cell mediated cytotoxicity
GO:0001914 regulation of T cell mediated cytotoxicity
GO:0001916 positive regulation of T cell mediated cytotoxicity
GO:0002228 natural killer cell mediated immunity
GO:0002237 response to molecule of bacterial origin
GO:0002250 adaptive immune response
GO:0002347 response to tumor cell
GO:0002407 dendritic cell chemotaxis
GO:0002418 immune response to tumor cell
GO:0002420 natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002423 natural killer cell mediated immune response to tumor cell
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002688 regulation of leukocyte chemotaxis
GO:0002690 positive regulation of leukocyte chemotaxis
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:0002709 regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002715 regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer 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:0002831 regulation of response to biotic stimulus
GO:0002833 positive regulation of response to biotic stimulus
GO:0002834 regulation of response to tumor cell
GO:0002836 positive regulation of response to tumor cell
GO:0002837 regulation of immune response to tumor cell
GO:0002839 positive regulation of immune response to tumor cell
GO:0002855 regulation of natural killer cell mediated immune response to tumor cell
GO:0002857 positive regulation of natural killer cell mediated immune response to tumor cell
GO:0002858 regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0007050 cell cycle arrest
GO:0007159 leukocyte cell-cell adhesion
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0009314 response to radiation
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0009615 response to virus
GO:0010224 response to UV-B
GO:0010657 muscle cell apoptotic process
GO:0010660 regulation of muscle cell apoptotic process
GO:0010661 positive regulation of muscle cell apoptotic process
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
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:0030335 positive regulation of cell migration
GO:0030595 leukocyte chemotaxis
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:0032496 response to lipopolysaccharide
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:0032700 negative regulation of interleukin-17 production
GO:0032729 positive regulation of interferon-gamma production
GO:0032814 regulation of natural killer cell activation
GO:0032816 positive regulation of natural killer cell activation
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0033002 muscle cell proliferation
GO:0034390 smooth muscle cell apoptotic process
GO:0034391 regulation of smooth muscle cell apoptotic process
GO:0034393 positive regulation of smooth muscle cell apoptotic process
GO:0036336 dendritic cell migration
GO:0040017 positive regulation of locomotion
GO:0042098 T cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T 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:0042504 tyrosine phosphorylation of Stat4 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042519 regulation of tyrosine phosphorylation of Stat4 protein
GO:0042520 positive regulation of tyrosine phosphorylation of Stat4 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0042742 defense response to bacterium
GO:0042832 defense response to protozoan
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045621 positive regulation of lymphocyte differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045786 negative regulation of cell cycle
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:0046631 alpha-beta T cell activation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046651 lymphocyte proliferation
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048662 negative regulation of smooth muscle cell proliferation
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050830 defense response to Gram-positive bacterium
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:0050900 leukocyte migration
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0051132 NK T cell activation
GO:0051133 regulation of NK T cell activation
GO:0051135 positive regulation of NK T cell activation
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051272 positive regulation of cellular component movement
GO:0060326 cell chemotaxis
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:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071396 cellular response to lipid
GO:0071593 lymphocyte aggregation
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097696 STAT cascade
GO:0098542 defense response to other organism
GO:0098586 cellular response to virus
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:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:2000147 positive regulation of cell motility
GO:2000508 regulation of dendritic cell chemotaxis
GO:2000510 positive regulation of dendritic cell chemotaxis
Molecular Function GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005143 interleukin-12 receptor binding
GO:0008083 growth factor activity
GO:0019955 cytokine binding
GO:0019972 interleukin-12 binding
GO:0019975 interleukin-17 binding
GO:0042163 interleukin-12 beta subunit binding
GO:0045513 interleukin-27 binding
GO:0046982 protein heterodimerization activity
GO:0070851 growth factor receptor binding
Cellular Component GO:0043514 interleukin-12 complex
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04620 Toll-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04630 Jak-STAT signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-6788467: IL-6-type cytokine receptor ligand interactions
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-447115: Interleukin-12 signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-6783589: Interleukin-6 family signaling
R-HSA-449147: Signaling by Interleukins
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IL12A 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 IL12A and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28223282Breast carcinoma; Colon Carcinoma; Lung carcinomaPromote immunity (T cell function)NKG2D-mediated immune surveillance is crucial for inhibiting tumor growth and metastases. High-profile studies have shown that restoring NKG2D ligand expression via genetic engineering inhibits tumor formation and progression. We found that co-administration of an immune stimulatory signal (interleukin-12) and chemotherapy (doxorubicin) restored the NKG2D ligand Rae-1 in multiple tumor types, including a human tumor model.
28191009Colon CarcinomaPromote immunityTwo prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively.
26939703Hepatocellular CarcinomaPromote immunity (NK cell function)Our results showed AR could suppress IL12A expression at the transcriptional level via direct binding to the IL12A promoter region that resulted in repressing efficacy of NK cell cytotoxicity against HCC, and sorafenib treatment could enhance IL12A signals via suppressing AR signals.
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.
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.
25329698LymphomaPromote immunity (NK cell function)Here, we found that treatments with IL-12 and IL-18 or with a mutant form of IL-2 (the "superkine" called H9) provided substantial therapeutic benefit for mice specifically bearing MHC class I-deficient tumors, but these treatments were ineffective for mice with matched MHC class I+ tumors. Cytokine efficacy was linked to the reversal of the anergic state of NK cells that specifically occurred in MHC class I-deficient tumors, but not MHC class I+ tumors.
10706701Colorectal adenocarcinomaPromote immunityInjection of AdCMVIP-10 into s.c. tumor nodules derived from the CT26 murine colorectal adenocarcinoma cell line displayed some antitumor activity but it was not curative in most cases. Importantly, intratumoral gene transfer with IL-12 and IP-10 generated a powerful tumor-specific CTL response in a synergistic fashion, while both CD4 and CD8 T cells appeared in the infiltrate of regressing tumors.
27655849Acute Myeloid LeukemiaPromote immunity; Essential for immunotherapyCytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation.
18354176Acute Myeloid LeukemiaPromote immunity (T cell function)This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15.
18272909Plasma Cell MyelomaPromote immunity (T cell function); essential for immunotherapyIdiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC). Eleven patients were immunized with the autologous Id in combinations with granulocyte-macrophage colony-stimulating factor and interleukin 12, and followed for CMC by quantitative real-time allele-specific PCR. Id vaccination reduced CMC, which correlated with vaccine-induced Id-specific T cells.
16517714NeuroblastomaPromote immunity (T and NK cell function); essential for immunotherapyWith the transduction of IL-12 and IL-18 genes into the fusion cells (fusion/IL-12/IL-18), the level of IFN-gamma increased more than five times that of other fusion groups. In addition, NK cell activity and CTL activity increased significantly compared with that of mixture/LacZ, fusion/LacZ, DC/LacZ, or C1300/LacZ.
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.
19688743MelanomaPromote immunity (T cell function)Gadd45b, a signaling molecule highly up-regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b(-/-) mice grew faster than those in WT or Gadd45b(+/-) littermate controls. The defect of Gadd45b(-/-) mice in tumor immunosurveillance was attributed to the reduced expression of IFN-gamma, granzyme B, and CCR5 in Gadd45b(-/-) CD8(+) T cells at the tumor site. Activation of p38 MAP kinase, but not ERK or JNK, by either TCR-stimuli or IL-12 and IL-18 is diminished in Gadd45b(-/-) CD8(+) T cells, resulting in reduced production of IFN-gamma.
19549770MelanomaPromote immunity (T cell function)DCs from melanoma-bearing mice secreted significantly more interleukin 10 and less interleukin 12p70, and showed a decreased capacity to activate T cells compared with DCs from tumor-free animals.
16778218MelanomaPromote immunity (T cell function)In vivo depletion assay revealed that the antitumor effect of B16/IL-23 was mainly mediated by CD8+ T cells and IFN-gamma whereas that of B16/IL-27 mainly involved natural killer cells and was independent of IFN-gamma. We also found that antitumor effects of B16/IL-23 and B16/IL-27 were synergistically enhanced by treatment with IL-18 and IL-12, respectively. Our data support that IL-23 and IL-27 might play a role in future cytokine-based immunotherapy against poorly immunogenic tumors.
16751376Breast CarcinomaPromote immunity (T cell function)A single intratumoral injection of IL-12 and GM-CSF-encapsulated microspheres induces the complete regression of advanced spontaneous tumors in her-2/neu transgenic mice. Posttherapy molecular analysis of immune activation/suppression markers within the tumor microenvironment demonstrated a dramatic up-regulation of IFN-gamma and a concomitant down-regulation of Forkhead/winged-helix protein 3 (Foxp3), TGFbeta, and IL-10 expression.
16651448LeukemiaPromote immunity (T cell function)The cytokine interleukin (IL)-12 promotes CD8(+) T-cell cytotoxicity and, with IL-18, synergistically up-regulates IFN-gamma release. We have shown that culturing CD8(+) T cells ex vivo with IL-12 and IL-18 enhanced antitumor responses in vivo and in vitro using a model of C1498/ovalbumin, a murine acute myeloid leukemia cell line expressing the antigen ovalbumin. Maximal IFN-gamma release occurred after T-cell culture with IL-12 and IL-18. Tumor-specific in vitro cytotoxicity was enhanced by IL-12, unaffected by addition of IL-18, and abrogated in perforin-deficient T cells irrespective of cytokine exposure.
16540672Lung CarcinomaPromote immunityA single intratracheal administration of CCL21 gene-modified dendritic cells (DC-AdCCL21) led to a marked reduction in tumor burden with extensive mononuclear cell infiltration of the tumors. The reduction in tumor burden was accompanied by the enhanced elaboration of type 1 cytokines [IFN-gamma, interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor] and antiangiogenic chemokines (CXCL9 and CXCL10) but a concomitant decrease in the immunosuppressive molecules (IL-10, transforming growth factor-beta, prostaglandin E(2)) in the tumor microenvironment. The DC-AdCCL21 therapy group revealed a significantly greater frequency of tumor-specific T cells releasing IFN-gamma compared with the controls.
23754388GlioblastomaPromote immunity (T cell function); essential for immunotherapyUsing this model, we tested a genetically engineered oncolytic herpes simplex virus that is armed with an immunomodulatory cytokine, interleukin 12 (G47-mIL12). G47Δ-mIL12 infects and replicates similarly to its unarmed oncolytic herpes simplex virus counterpart in mouse 005 GSCs in vitro, whereas in vivo, it significantly enhances survival in syngeneic mice bearing intracerebral 005 tumors. Mechanistically, G47-mIL12 targets not only GSCs but also increases IFN-γ release, inhibits angiogenesis, and reduces the number of regulatory T cells in the tumor.
22360982B16 Malignant MelanomaEssential for immunotherapyAdoptive transfer of tumor-specific CD8(+) T cells primed with IL-12 was significantly more effective in reducing tumor burden in mice preconditioned with cyclophosphamide compared with transfer of T cells primed without IL-12. This enhanced antitumor response was associated with increased frequencies of infused T cells in the periphery and tumor as well as elevated expression of effector molecules including granzyme B and interferon-γ (IFNγ).
17326190Liver CarcinomaPromote immunity (NK cell function); essential for immunotherapyOur results demonstrated that IL-12, but not GM-CSF, monotherapy displayed significant therapeutic effects, whereas combination therapy with both cytokines displayed synergistic antitumor effects not only on transplanted tumor models with intermediate or large tumor loads, but also on carcinogen-induced multifocal liver tumors. Effector cell analyses, revealed by in vivo cell subset depletion, flow cytometry analysis, and immunohistochemical staining of tumor infiltrates, indicated that NK cells were the prominent antitumor effectors for the IL-12-mediated antitumor activity, whereas CD8+ T cells, NKT cells, and macrophages were more important than NK cells in the combination therapy-mediated antitumor effects
24789737Lung CarcinomaPromote immunityOverexpression of miR-301a in DCs suppressed IL-12 secretion, decreased IFN-γ release from antigen-specific cytotoxic T cells, and shifted antigen-specific T helper cytokine profile away from IFN-γ towards IL-13 and IL-17A-secreting T cells.
20935648MelanomaPromote immunity (T cell function)IL-12 initiated local antitumor immunity by stimulating a subset of NKp46(+) lymphoid tissue-inducer (LTi) cells dependent on the transcription factor RORγt. The presence of these NKp46(+) LTi cells induced upregulation of adhesion molecules in the tumor vasculature and resulted in more leukocyte invasion.
29453519Tongue Squamous Cell Carcinoma; Lung CarcinomaPromote immunity (infiltration)Neutralizing IL12 signaling with an IL12 antibody abrogated TriCurin-induced intra-tumor entry of activated natural killer (NK) cells and Cytotoxic T lymphocytes (CTL), thereby confirming that IL12 triggers recruitment of NK cells and CTL. These activated NK cells and CTL join the M1 TAM to elicit apoptosis of the E6+?tumor cells. Corroboratively, neutralizing IL12 signaling partially reversed this TriCurin-mediated apoptosis
17237382Lung CarcinomaPromote immunity (T cell function)Analysis of tumor-infiltrating macrophages and distal TAMs revealed that IL-12, both in vivo and in vitro, induced a rapid (<90 min) reduction of tumor supportive macrophage activities (IL-10, MCP-1, migration inhibitory factor, and TGFbeta production) and a concomitant increase in proinflammatory and proimmunogenic activities (TNF-alpha, IL-15, and IL-18 production). Similar shifts in functional phenotype were induced by IL-12 in tumor-infiltrating macrophages isolated from the primary tumor mass and in TAMs isolated from lung containing metastases, spleen, and peritoneal cavity.
21515097Colorectal Cancinoma; Pancreatic CarcinomaPromote immunityWe previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population.
21447719Renal Cell Carcinoma; MelanomaPromote immunityAS1409 is a fusion protein comprising a humanized antibody BC1 linked to interleukin-12 (IL-12). IFN-γ and interferon-inducible protein-10 (IP-10) were elevated in all patients, indicating activation of cell-mediated immune response; this was attenuated at subsequent cycles.
21430221MelanomaPromote immunity (T cell function)In vitro priming of mouse tumor-specific CD8(+) T cells in the presence of IL-12 induced a diverse and rapid antitumor effector activity while still promoting the generation of memory cells.
18537185Hepatocellular CarcinomaPromote immunityAd-CD40L transduction exerted CD40/CD40L interactions between DCs, increasing DC immunostimulation with up-regulation of CD80/CD86- and interleukin-12 (IL-12) expression.
18478568MelanomaPromote immunityTherefore the p44/42 MAPK is a target for tumour-mediated immune suppression of DC resulting in transcriptional down-regulation of IL-12 p35 and p40 genes, reduced IL-12 secretion and suppressed Th1-responses.
15947685Bladder CarcinomaPromote immunityThe inhibition of PGE2 synthesis by COX inhibition favored the production of IL-12 by BCG activated DC. This potentially will result in the generation of a T-helper type 1, polarized T-cell response that may improve the efficacy of BCG therapy.
25229656Cervical CarcinomaPromote immunity (NK cell function)IL-12p70 stimulates NK cells to produce IFN-γ [62] and close contacts between NK cells and DCs are necessary to reach the level of concentration allowing NK-cell activation
25205103lymphomaPromote immunityRecombinant HMGN1 induced the accumulation and activation of DCs at the site of injection as indicated by upregulation of costimulatory and MHC molecules as well as extracellular secretion of proinflammatory cytokines such as TNFa, IL12 p70, and IL1b
23333935Prostate Carcinoma; Colon CarcinomaPromote immunityThe enhanced tumor destruction is accompanied with significantly increased tumor infiltration by CD8(+) cells as well as elevation of IFN-gamma and interleukin (IL)-12 levels in the tumor sites.
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.
21949133Lung CarcinomaPromote immunityIncreased apoptosis, the induction of cytokines (IFN-γ and IL-12) and chemokines (CXCL9 and CXCL10), and the elevation of leukocyte markers (CD11b, CD11c, CD4, and CD8) were detected at tumor sites in C3H/HeN mice but not in C3H/HeJ mice
21908736Breast CarcinomaPromote immunityIntratumoral delivery of IL-12 and GM-CSF induces local and systemic antitumor CD8(+) T cell activation and tumor kill.
16920987pancreatic carcinomaPromote immunityMedium conditioned by human pancreatic carcinoma cells inhibited iMo-DC proliferation, expression of costimulatory molecules (CD80 and CD40) and of HLA-DR, and functional activity as assessed by MLR and IL-12p70 production. iMo-DC generated from pancreatic carcinoma patients in advanced stages of the disease similarly showed decreased levels of HLA-DR expression and reduced ability to stimulate MLR in response to CD40L and IFN-gamma.
16844772MelanomaPromote immunityWe find that a recently described analogue, alpha-C-galactosylceramide (alpha-C-GalCer), more potently induces these innate and adaptive immune responses in mice. alpha-C-GalCer acts as a more effective trigger for IL-12 and IFN-gamma production, although it minimally elicits IL-4 and TNF-alpha release into the serum. Also, alpha-C-GalCer better mobilizes NKT and natural killer cells to resist B16 melanoma.
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
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 IL12A 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
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
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 IL12A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.2730.288
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3070.52
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2550.5
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3840.641
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1720.89
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6520.644
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.8150.149
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4530.644
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11121.3270.237
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0270.953
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4440.505
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0520.767
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IL12A 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) 277311.11.49.70.0589
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.11.79.40.0895
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) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
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
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL12A. 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
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL12A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL12A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL12A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IL12A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IL12A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIL12A
Nameinterleukin 12A
Aliases IL-12A; NFSK; natural killer cell stimulatory factor 1, 35 kD subunit; cytotoxic lymphocyte maturation facto ......
Chromosomal Location3q25.33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IL12A collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.