TISIDB

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
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 [ TOP ]
Subcellular Location	Secreted Note=Does not seem to be secreted without coexpression of EBI3.
Domain	-
Function	Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction. IL-27 potentiate the early phase of TH1 response and suppress TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment. It suppresses the expression of GATA3, the inhibitor TH1 cells development. In CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the development of proinflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, iTreg, independently of STAT1. IL-27 has also an effect on cytokine production, it suppresses proinflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T-cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9. In vein endothelial cells, it induces IRF1/interferon regulatory factor 1 and increase the expression of MHC class II transactivator/CIITA with resulting up-regulation of major histocompatibility complex class II. IL-27 also demonstrates antiviral activity with inhibitory properties on HIV-1 replication.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002286 T cell activation involved in immune response GO:0002287 alpha-beta T cell activation involved in immune response GO:0002292 T cell differentiation involved in immune response GO:0002293 alpha-beta T cell differentiation involved in immune response GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation GO:0002694 regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002819 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:0002825 regulation of T-helper 1 type immune response GO:0002831 regulation of response to biotic stimulus GO:0007159 leukocyte cell-cell adhesion GO:0009615 response to virus GO:0022407 regulation of cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0032609 interferon-gamma production GO:0032649 regulation of interferon-gamma production GO:0032729 positive regulation of interferon-gamma production GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0035710 CD4-positive, alpha-beta T cell activation GO:0042035 regulation of cytokine biosynthetic process GO:0042088 T-helper 1 type immune response GO:0042089 cytokine biosynthetic process GO:0042093 T-helper cell differentiation GO:0042095 interferon-gamma biosynthetic process GO:0042098 T cell proliferation GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0043367 CD4-positive, alpha-beta T cell differentiation GO:0043370 regulation of CD4-positive, alpha-beta T cell differentiation GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0045063 T-helper 1 cell differentiation GO:0045072 regulation of interferon-gamma biosynthetic process GO:0045078 positive regulation of interferon-gamma biosynthetic process GO:0045580 regulation of T cell differentiation GO:0045619 regulation of lymphocyte differentiation GO:0045622 regulation of T-helper cell differentiation GO:0045625 regulation of T-helper 1 cell differentiation GO:0046631 alpha-beta T cell activation GO:0046632 alpha-beta T cell differentiation GO:0046634 regulation of alpha-beta T cell activation GO:0046637 regulation of alpha-beta T cell differentiation GO:0046651 lymphocyte proliferation GO:0050670 regulation of lymphocyte proliferation GO:0050688 regulation of defense response to virus GO:0050792 regulation of viral process GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0051249 regulation of lymphocyte activation GO:0051607 defense response to virus GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0098542 defense response to other organism GO:1902105 regulation of leukocyte differentiation GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903706 regulation of hemopoiesis GO:2000514 regulation of CD4-positive, alpha-beta T cell activation
Molecular Function	GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0045523 interleukin-27 receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
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-6783589: Interleukin-6 family signaling R-HSA-449147: Signaling by Interleukins

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL27 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

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Literatures describing the relation between IL27 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25614966	Melanoma	Inhibit immunity (T cell function)	Thus, our data identify an IL-27/NFIL3 signalling axis as a key regulator of effector T-cell responses via induction of Tim-3, IL-10 and T-cell dysfunction.
22678911	Breast Carcinoma	Inhibit immunity (T cell function)	Immunosuppression via Treg cells was transferable and required the release of sphingosine-1-phosphate (S1P) from apoptotic cells, acting via S1P receptor 4 on DCs to induce IL-27 secretion. We propose that CD69 expression on CD39(+) Treg cells enables them to interact with CD73-expressing CD8(+) T cells to generate adenosine, thereby suppressing cytotoxicity.
18453571	Melanoma	Promote immunity (T and NK cell function); essential for immunotherapy	Antiproliferative activity of IL-27 on melanoma. We previously demonstrated that IL-27 has potent antitumor activities, which are mediated through CD8(+) T cells, NK cells, or its own antiangiogenic activity. Although WSX-1 expression was hardly detected in parental mouse melanoma B16F10 cells, IL-27 activated STAT1 and STAT3 and up-regulated MHC class I in B16F10 transfectants expressing wild-type WSX-1. Thus, IL-27 may be an attractive candidate as an antitumor agent applicable to cancer immunotherapy.
16778218	Melanoma	Promote 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.
16751375	Lung Carcinoma	Promote immunity	Similar antitumor and antimetastatic activities of IL-27 were also observed in IFN-gamma knockout mice. Immunohistochemical analyses with Abs against vascular endothelial growth factor and CD31 revealed that B16F10 + IL-27 cells markedly suppressed tumor-induced neovascularization in lung metastases. IL-27 was revealed to directly act on HUVECs and induce production of the antiangiogenic chemokines, IFN-gamma-inducible protein (IP-10) and monokine induced by IFN-gamma. Finally, augmented mRNA expression of IP-10 and monokine induced by IFN-gamma was detected at the s.c.
23873689	Ovarian Cancinoma	Promote immunity	In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation.
29487200	Prostate Carcinoma	Inhibit immunity; candidate for immunotherapy target	Interleukin-30/IL-27p28 shapes prostate cancer stem-like cell behavior and is critical for tumor onset and metastasization. PCSLC-derived IL-30 supported PCSLC viability, self-renewal and tumorigenicity, expression of inflammatory mediators and growth factors, tumor immune evasion and regulated chemokine and chemokine receptor genes, primarily via STAT1/STAT3 signaling. Furthermore, it promoted PCSLC dissemination to lymph nodes and bone marrow by upregulating the CXCR5/CXCL13 axis, and drove metastasis to lungs through the CXCR4/CXCL12 axis.
24443555	Melanoma	Inhibit immunity	A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells. Tumor-associated DCs were identified as the major source of CCL22 in tumor sites, and IL-27 could induce CCL22 expression in an IL-27R-dependent manner.
23225163	plasmacytoma	Promote immunity	While STAT3 activation and the CTL survival-enhancing effects can be independent of CTL IL-10 production, we show here that IL-27-induced CTL IL-10 production contributes to memory precursor cell phenotype induction, CTL memory, and tumor rejection.

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
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

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Statistical results of IL27 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
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

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Points in the above scatter plot represent the expression difference of IL27 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.054	0.818
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.348	0.423
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.164	0.664
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.15	0.839
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.453	0.74
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.238	0.877
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.019	0.973
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.443	0.55
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.064	0.735

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL27 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL27. 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 [ TOP ]

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL27. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL27. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL27. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL27 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL27 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL27
Name	interleukin 27
Aliases	IL27p28; IL-27A; IL27A; MGC71873; IL30; interleukin 30; IL-27AA; IL-27 p28 subunit; IL-27 subunit alpha; IL- ......
Chromosomal Location	16p11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL27 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse IL27