Browse IL15

Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
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 Isoform IL15-S48AA: Secreted.; SUBCELLULAR LOCATION: Isoform IL15-S21AA: Cytoplasm. Nucleus. Note=IL15-S21AA is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components.
Domain PF02372 Interleukin 15
Function

Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha.

> Gene Ontology
 
Biological Process GO:0001779 natural killer cell differentiation
GO:0001787 natural killer cell proliferation
GO:0001819 positive regulation of cytokine production
GO:0001866 NK T cell proliferation
GO:0002521 leukocyte differentiation
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002831 regulation of response to biotic stimulus
GO:0003012 muscle system process
GO:0006022 aminoglycan metabolic process
GO:0006486 protein glycosylation
GO:0006493 protein O-linked glycosylation
GO:0007159 leukocyte cell-cell adhesion
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0007568 aging
GO:0007584 response to nutrient
GO:0009100 glycoprotein metabolic process
GO:0009101 glycoprotein biosynthetic process
GO:0009615 response to virus
GO:0009991 response to extracellular stimulus
GO:0010559 regulation of glycoprotein biosynthetic process
GO:0010560 positive regulation of glycoprotein biosynthetic process
GO:0014732 skeletal muscle atrophy
GO:0014888 striated muscle adaptation
GO:0014889 muscle atrophy
GO:0014891 striated muscle atrophy
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0021700 developmental maturation
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030101 natural killer cell activation
GO:0030203 glycosaminoglycan metabolic process
GO:0030212 hyaluronan metabolic process
GO:0030217 T cell differentiation
GO:0031349 positive regulation of defense response
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0031670 cellular response to nutrient
GO:0032103 positive regulation of response to external stimulus
GO:0032620 interleukin-17 production
GO:0032660 regulation of interleukin-17 production
GO:0032740 positive regulation of interleukin-17 production
GO:0032814 regulation of natural killer cell activation
GO:0032816 positive regulation of natural killer cell activation
GO:0032817 regulation of natural killer cell proliferation
GO:0032819 positive regulation of natural killer cell proliferation
GO:0032823 regulation of natural killer cell differentiation
GO:0032825 positive regulation of natural killer cell differentiation
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:0033078 extrathymic T cell differentiation
GO:0033273 response to vitamin
GO:0033280 response to vitamin D
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
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:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042506 tyrosine phosphorylation of Stat5 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043413 macromolecule glycosylation
GO:0043500 muscle adaptation
GO:0043501 skeletal muscle adaptation
GO:0043900 regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0045058 T cell selection
GO:0045062 extrathymic T cell selection
GO:0045580 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:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046631 alpha-beta T cell activation
GO:0046633 alpha-beta T cell proliferation
GO:0046651 lymphocyte proliferation
GO:0048469 cell maturation
GO:0048535 lymph node development
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048662 negative regulation of smooth muscle cell proliferation
GO:0048771 tissue remodeling
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050688 regulation of defense response to virus
GO:0050691 regulation of defense response to virus by host
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050792 regulation of viral process
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:0051132 NK T cell activation
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051607 defense response to virus
GO:0060049 regulation of protein glycosylation
GO:0060050 positive regulation of protein glycosylation
GO:0070085 glycosylation
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:0071295 cellular response to vitamin
GO:0071305 cellular response to vitamin D
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071496 cellular response to external stimulus
GO:0071593 lymphocyte aggregation
GO:0097696 STAT cascade
GO:0098542 defense response to other organism
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1903018 regulation of glycoprotein metabolic process
GO:1903020 positive regulation of glycoprotein metabolic process
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903510 mucopolysaccharide metabolic process
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904098 regulation of protein O-linked glycosylation
GO:1904100 positive regulation of protein O-linked glycosylation
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
Molecular Function GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04630 Jak-STAT signaling pathway
hsa04668 TNF signaling pathway
hsa04672 Intestinal immune network for IgA production
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-449147: Signaling by Interleukins
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IL15 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 IL15 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26511282Melanoma; Colon CarcinomaPromote immunity (T cell function)IL15, a potent stimulant of CD8(+) T cells and natural killer (NK) cells, is a promising cancer immunotherapeutic.
27213690Melanoma; Prostate Carcinoma; Breast CarcinomaInhibit immunity (NK cell function)We identified cytokine-inducible SH2-containing protein (CIS, encoded by Cish) as a critical negative regulator of IL-15 signaling in NK cells. Cish was rapidly induced in response to IL-15, and deletion of Cish rendered NK cells hypersensitive to IL-15, as evidenced by enhanced proliferation, survival, IFN-γ production and cytotoxicity toward tumors.
26423796LymphomaPromote immunity (NK cell function)ALT-803 is a superagonist IL-15 mutant and IL-15Rα-Fc fusion complex that activates the IL-15 receptor constitutively expressed on natural killer (NK) cells. ALT-803 augmented cytotoxicity and the expression of granzyme B and perforin, providing one potential mechanism for this enhanced functionality.
26174883GlioblastomaPromote immunity (infiltration); increase the efficacy of immunotherapyWe show that an IL-15 superagonist complex ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice.
25601928Colon AdenocarcinomaPromote immunity (T cell function)In vivo 4-1BB deficiency in myeloid cells enhances peripheral T cell proliferation by increasing IL-15.
25403209MelanomaPromote immunity (T cell function)Interleukin-15 (IL-15) has significant potential in cancer immunotherapy as an activator of antitumor CD8 T and natural killer (NK) cells.
22585684MelanomaPromote immunity (NK cell function)Analysis of different NK-cell-activating cytokines indicated that IL-15 can partially overcome this novel tumor escape mechanism suggesting that IL-15, rather than IL-2, may be eligible for NK-cell-based immunotherapy.
22565311NeuroblastomaPromote immunity (T cell function)Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15-transduced NKT cells.
22532287Small Cell Lung CarcinomaInhibit immunityOur data suggest that IL-15 and Treg cells are potential new therapeutic targets to improve immune response and patient survival in SCLC.
22474386Prostate CarcinomaPromote immunityCombining the immune stimulatory properties of IL-15 with simultaneous removal of two critical immune inhibitory checkpoints, we showed enhancement of immune responses, leading to increased antitumor activity.
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.
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.
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.
18413767MelanomaPromote immunity (T cell function); essential for immunotherapyInterleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Our data provide novel insights into the use of IL-15/IL-15R alpha complexes to relieve tumor-resident T cells from functional suppression by the tumor microenvironment and have significant implications for cancer immunotherapy and treatment of chronic infections.
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.
18275895Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Myelodysplastic Syndrome; MyelofibrosisPromote immunity (NK cell function)Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Furthermore, in NK cells cultured with IL-15, we observed an up-regulation of the activating receptors NKG2D, NKp30, and NKp46, associated with an increase in anti-tumor lytic activity.
16474399LeukemiaPromote immunity (T cell function); essential for immunotherapyInterleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Such proliferation abrogated tolerance and the rescued cells became effective in treating leukemia.
23149919MelanomaPromote immunity (T cell function; NK cell function)Sushi-IL-15-Apo as a recombinant protein was also bioactive in vivo, became conjugated to HDL, and displayed immunotherapeutic effects against metastatic disease.
23149818Hodgkin lymphomaPromote immunity (T cell function)We found that in the presence of Tregs, IL-15, but not IL-2, promoted the proliferation, effector function, and resistance to apoptosis of effectors T cells and EBV-CTLs. IL-15 did not reverse or block Tregs but instead preferentially supported the proliferation of CTLs and effector T cells as compared with Tregs.
22981349Kidney carcinomaPromote immunity (T cell function)By contrast, during allograft rejection, the increased intra-graft IL-15 expression favors tubular destruction facilitating the intraepithelial recruitment of CD8 T cells expressing the E-cadherin ligand CD103. In renal cancer, loss of CD132 by epithelial cells defines a tumoral microenvironment where IL-15 triggers E-cadherin down-regulation and EMT.
28550091GliomaPromote immunityNo autonomous IL13Rα2-CAR.IL15 T-cell proliferation was observed; however, IL15 expression increased IL13Rα2-CAR T-cell viability in the absence of exogenous cytokines or antigen.In vivo, IL13Rα2-CAR.IL15 T cells persisted longer and had greater antiglioma activity than IL13Rα2-CAR T cells, resulting in a survival advantage.
16788095LeukemiaInhibit immunity (T cell function)CD8+ memory T cells, as defined by CD44(hi) surface expression, are dependent on IL-15 as a positive regulator of their homeostatic maintenance. Manipulation of IL-15 signaling through gene aberration, overexpression, or receptor alterations has been shown to dramatically affect T-cell homeostasis, with overexpression leading to fatal leukemia. Here we show that TGF-beta is the critical negative regulator of murine CD8+ memory T-cell homeostasis with direct opposition to the positive effects of IL-15.
16621991MelanomaPromote 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.
16621962LymphomaPromote immunity (T cell function)ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15. ULBPs are human ligands for NKG2D, an activating receptor expressed on natural killer (NK) cells, NK1.1(+) T cells, and T cells. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors.
27465917B-cell LymphomaPromote immunity (T cell function)IL-15 augmented mammalian target of rapamycin (mTOR) signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK-cell function during cytokine activation but not following cytokine withdrawal. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B-cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR-regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy.
25016226hepatocellular carcinomaPromote immunity (T cell function); increase the efficacy of immunotherapyHere, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor α chain, on metastatic and autochthonous liver cancers.
24928851Pancreatic CarcinomaPromote immunityIn vitro assays of lymphocyte activation and proliferation demonstrated that IL15 produced by MSCs was biofunctional.
29664568melanomaPromote immunity (T cell function); essential for immunotherapyThese phases of a T-cell response and the ensuing maintenance of memory T cells are shaped by cytokines, most notably interleukin-2 (IL-2), IL-7, and IL-15 that share the common γ chain (γc ) cytokine receptor.
29599411melanomaPromote immunity (T cell function); increase the efficacy of immunotherapyLocal IL15 expression levels strongly correlated with these tumor-resident T-cell numbers.
24016461Acute Myeloid Leukemia; Plasma Cell MyelomaEssential for immunotherapyAccordingly, T cells targeted to CD44v6 by means of a chimeric antigen receptor containing a CD28 signaling domain mediated potent antitumor effects against primary AML and MM while sparing normal hematopoietic stem cells and CD44v6-expressing keratinocytes. Importantly, in vitro activation with CD3/CD28 beads and interleukin (IL)-7/IL-15 was required for antitumor efficacy in vivo.
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.
21355077MelanomaPromote immunity (T cell function)We compared the efficacy of human Langerhans cells (LC) as tumor immunogens in vivo with monocyte-derived dendritic cells (moDC) and investigated how interleukin 15 (IL15) supports optimal DC-stimulated antitumor immunity. IL15 promotes T-cell expression of the antiapoptotic bcl-2 and inhibits candidate regulatory T-cell (Treg) expansion after DC stimulation, countering two effects of IL2 that do not foster tumor immunity.
21317394Lung NeoplasmPromote immunity (NK cell function)Taken altogether, our data suggest that NK cell adoptive transfer can trigger adaptive antitumor T cell responses, and regulatory T cell depletion by Ontak is mandatory for enabling HC/IL-15-activated NK cells to promote long-lasting adaptive antitumor immunity.
19949105MelanomaPromote immunityAn analysis of different supportive cytokine mixtures during the REP found that a combination of IL-15 and IL-21 facilitated comparable expansion of CD8(+) TILs as IL-2, but prevented the loss of CD28 expression with improved responsiveness to antigenic restimulation post-REP. A REP protocol using IL-15 and IL-21 may greatly increase the number of CD28(+) TILs capable of long-term persistence.
19949105MelanomaPromote immunityAn analysis of different supportive cytokine mixtures during the REP found that a combination of IL-15 and IL-21 facilitated comparable expansion of CD8(+) TILs as IL-2, but prevented the loss of CD28 expression with improved responsiveness to antigenic restimulation post-REP. A REP protocol using IL-15 and IL-21 may greatly increase the number of CD28(+) TILs capable of long-term persistence.
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.
29224228B16 Malignant MelanomaPromote immunity (T cell function); essential for immunotherapyThe cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro. Interleukin 15 (IL15) and IL7 are two cytokines essential for T cell development and homeostasis. Taken together, our data strongly indicated that tumor vaccine modified with NDV strain LX/IL(15+7) is a promising agent for cancer immunotherapy.
15951291Acute Lymphoblastic LeukemiaPromote immunity (NK cell function)Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission. In addition, incubating these effectors for 24 hours with IL-2 + IL-15 significantly increased this cytotoxic function.
28811289MelanomaPromote immunityPrimary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells. The combined analysis of these approaches allowed us to establish a hierarchy in which patrolling monocytes, making IL15 in response to primary tumors, activate NK cells and IFNγ production that then inhibit lung metastasis formation. Critically, the protective effect on metastasis was lost upon patrolling monocyte or NK cell depletion, IL15 neutralization, or IFNγ ablation.
24415778Colorectal CarcinomaPromote immunityImportantly, immunity to metastasis formation could also be restored in T-bet-deficient recipients by treating mice with IL-15 precomplexed to IL-15 receptor-α, which induced the development of eomesodermin(+)KLRG1(+) NK cells from existing NK cell populations.
29737430LeukemiaPromote immunityhIL-15-gene modified human natural killer cells (NKL-IL15) exhibit anti-human leukemia functions. We found NKL-IL15 cells displayed a significant high cytolysis activity against both human leukemia cell lines and primary leukemia cells from patients, accompanied with up-regulated expression of molecules related to NK cell cytotoxicity such as perforin, granzyme B and NKp80. Moreover, cytokines secreted by NKL-IL15 cells, including TNF-α and IFN-γ, could induce the expression of NKG2D ligands on target cells, which increased the susceptibility of leukemia cells to NK cell-mediated cytolysis.
29692776Acute Myeloid LeukemiaPromote immunityInterleukin-15-Cultured Dendritic Cells Enhance Anti-Tumor Gamma Delta T Cell Functions through IL-15 Secretion. IL-15 DCs of healthy donors and of AML patients in remission induce the upregulation of cytotoxicity-associated and co-stimulatory molecules on the γδ T cell surface, but not of co-inhibitory molecules, incite γδ T cell proliferation and stimulate their interferon-γ production in the presence of blood cancer cells and phosphoantigens. Moreover, the innate cytotoxic capacity of γδ T cells is significantly enhanced upon interaction with IL-15 DCs, both towards leukemic cell lines and allogeneic primary AML blasts.
29691234Plasma Cell MyelomaPromote immunityThe increased IL15 was accompanied by enhanced expression of the IL15/IL15RA complex on the membrane of senescent myeloma cells, allowing the functional trans-presentation of this cytokine to neighboring NK cells, which consequently underwent activation and proliferation. We demonstrated that MM cell-derived exosomes, the release of which was augmented by melphalan (MEL) treatment in senescent cells, also expressed IL15RA and IL15, and their interaction with NK cells in the presence of exogenous IL15 resulted in increased proliferation.
25200249melanomaPromote immunityThis is consistent with the observations by us and others that IL-21 alone did not drive a large expansion of CD8+ T cells but synergized with IL-7 or IL-15 to promote CD8+ T cell proliferation while curtailing acquisition of a hypo-proliferative terminally-differentiated phenotype [101,102].
25060519NeuroblastomaPromote immunityWhen used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, whereas the intratumoral release of both RANTES and IL15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor-bearing mice.
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.
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.
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
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 IL15 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
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
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 IL15 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1670.679
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0830.918
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.3540.569
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.4090.478
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4880.615
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3080.782
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1360.757
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5460.474
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3650.669
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.0740.446
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9650.635
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0070.962
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IL15 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) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
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
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL15. 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
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL15. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL15.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL15. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IL15 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IL15 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIL15
Nameinterleukin 15
Aliases IL-15; MGC9721; Interleukin-15
Chromosomal Location4q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IL15 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting IL15.
ID Name Drug Type Targets #Targets
DB01327CefazolinSmall MoleculeIL15, IL2, PON13