TISIDB

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
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	Nucleus Chromosome Cytoplasmic vesicle, secretory vesicle Secreted Note=Associates with heterochromatin and mitotic chromosomes (PubMed:17185418).
Domain	PF15095 Interleukin 33
Function	Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury (PubMed:17853410, PubMed:18836528). ; FUNCTION: In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets (PubMed:21734074). This form is rapidely lost upon angiogenic or proinflammatory activation (PubMed:18787100).

> Gene Ontology [ TOP ]
Biological Process	GO:0001774 microglial cell activation GO:0001818 negative regulation of cytokine production GO:0001819 positive regulation of cytokine production GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002274 myeloid leukocyte activation GO:0002275 myeloid cell activation involved in immune response GO:0002281 macrophage activation involved in immune response GO:0002282 microglial cell activation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002377 immunoglobulin production GO:0002440 production of molecular mediator of immune response GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002637 regulation of immunoglobulin production GO:0002638 negative regulation of immunoglobulin production GO:0002639 positive regulation of immunoglobulin production GO:0002683 negative regulation of immune system process GO:0002685 regulation of leukocyte migration GO:0002686 negative regulation of leukocyte migration GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002698 negative 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:0002701 negative regulation of production of molecular mediator of immune response GO:0002702 positive regulation of production of molecular mediator of immune response GO:0002819 regulation of adaptive immune response GO:0002820 negative 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:0002823 negative 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:0002826 negative regulation of T-helper 1 type immune response GO:0002828 regulation of type 2 immune response GO:0002830 positive regulation of type 2 immune response GO:0009306 protein secretion GO:0009615 response to virus GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010498 proteasomal protein catabolic process GO:0014009 glial cell proliferation GO:0030336 negative regulation of cell migration GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0031349 positive regulation of defense response GO:0032103 positive regulation of response to external stimulus GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032602 chemokine production GO:0032609 interferon-gamma production GO:0032616 interleukin-13 production GO:0032633 interleukin-4 production GO:0032634 interleukin-5 production GO:0032635 interleukin-6 production GO:0032642 regulation of chemokine production GO:0032649 regulation of interferon-gamma production GO:0032656 regulation of interleukin-13 production GO:0032673 regulation of interleukin-4 production GO:0032674 regulation of interleukin-5 production GO:0032675 regulation of interleukin-6 production GO:0032689 negative regulation of interferon-gamma production GO:0032722 positive regulation of chemokine production GO:0032736 positive regulation of interleukin-13 production GO:0032753 positive regulation of interleukin-4 production GO:0032754 positive regulation of interleukin-5 production GO:0032755 positive regulation of interleukin-6 production GO:0040013 negative regulation of locomotion GO:0042063 gliogenesis GO:0042088 T-helper 1 type immune response GO:0042092 type 2 immune response GO:0042116 macrophage activation GO:0042176 regulation of protein catabolic process GO:0043030 regulation of macrophage activation GO:0043032 positive regulation of macrophage activation GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045732 positive regulation of protein catabolic process GO:0045862 positive regulation of proteolysis GO:0048305 immunoglobulin secretion GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050709 negative regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050777 negative regulation of immune response GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050900 leukocyte migration GO:0051023 regulation of immunoglobulin secretion GO:0051024 positive regulation of immunoglobulin secretion GO:0051025 negative regulation of immunoglobulin secretion GO:0051047 positive regulation of secretion GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051222 positive regulation of protein transport GO:0051224 negative regulation of protein transport GO:0051271 negative regulation of cellular component movement GO:0051607 defense response to virus GO:0061136 regulation of proteasomal protein catabolic process GO:0061517 macrophage proliferation GO:0061518 microglial cell proliferation GO:0070661 leukocyte proliferation GO:0090195 chemokine secretion GO:0090196 regulation of chemokine secretion GO:0090197 positive regulation of chemokine secretion GO:0097191 extrinsic apoptotic signaling pathway GO:0098542 defense response to other organism GO:1901800 positive regulation of proteasomal protein catabolic process GO:1903050 regulation of proteolysis involved in cellular protein catabolic process GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process GO:1903362 regulation of cellular protein catabolic process GO:1903364 positive regulation of cellular protein catabolic process GO:1903531 negative regulation of secretion by cell GO:1903532 positive regulation of secretion by cell GO:1904950 negative regulation of establishment of protein localization GO:1904951 positive regulation of establishment of protein localization GO:2000146 negative regulation of cell motility
Molecular Function	GO:0005125 cytokine activity
Cellular Component	GO:0030133 transport vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04623 Cytosolic DNA-sensing pathway
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-5688426: Deubiquitination R-HSA-168256: Immune System R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-449147: Signaling by Interleukins R-HSA-5689880: Ub-specific processing proteases

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL33 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 IL33 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28249897	Colon Carcinoma	Promote immunity (infiltration)	Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth.
25429071	Melanoma	Promote immunity (T cell function)	Mechanistically, IL-33 increased numbers and IFN-γ production by CD8(+) T and NK cells in tumor tissues, thereby inducing a tumor microenvironment favoring tumor eradication.
28548102	Thymoma; Mastocytoma	Promote immunity	Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTLeffinflux triggers an inflammatory conversion of the tumour microenvironment.
24778632	Breast Carcinoma	Inhibit immunity	Murine breast carcinoma models suggest disruption of ST2 signaling may enhance the anti-tumor immune response, suggesting IL-33 impedes anti-tumor immunity. However, the role of IL-33 in patients with breast cancers (BC) is not elucidated. Murine breast carcinoma models suggest disruption of ST2 signaling may enhance the anti-tumor immune response, suggesting IL-33 impedes anti-tumor immunity. However, the role of IL-33 in patients with breast cancers (BC) is not elucidated. We detected the expression of IL-33 in tumor tissue, and IL-33 and its related cytokines in serum from BC patients. Using Luminex and immunohistochemistry methods, we found that serum levels of IL-33 were nearly twofold higher in patients with BC, compared to patients with benign breast diseases. In cancer tissues, expression of IL-33 was higher than matched normal breast tissues from the same patients, and was also associated with a well-differentiated phenotype, HER2 overexpression, more lymph nodes involvement, and a family history of malignant carcinoma.
29440650	Hepatocellular Carcinoma	Promote immunity (infiltration)	Our data support the model that IL-33 dependent tumour-infiltrating ILC2s are mobilized from the lungs and other tissues through chemoattraction to enter tumours, and subsequently mediate tumour immune-surveillance by cooperating with dendritic cells to promote adaptive cytolytic T cell responses.
29463593	Colon Carcinoma	Promote immunity	The decrease of this IFNγ gene expression signature was associated with more aggressive disease in human colon cancer patients, suggesting that lack of IL33 signaling impaired the generation of a potent IFNγ-mediated antitumor immune response. Collectively, our data reveal that IL33 functions as a tumor suppressor in sporadic colon cancer.
29208683	Squamous Cell Carcinoma	Inhibit immunity	IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through transcriptional networks. IL-33 associated with FAK in the nucleus, and the FAK-IL-33 complex interacted with a network of chromatin modifiers and transcriptional regulators, including TAF9, WDR82, and BRD4, which promote the activity of nuclear factor κB (NF-κB) and its induction of genes encoding chemokines, including CCL5.
28011934	Melanoma	Promote immunity	We show that exogenous IL-33 can induce robust antitumor effect through a CD8+T cell-dependent mechanism. Notably, in addition to a direct action on CD8+T cell expansion and IFN-γ production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment.

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
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 IL33 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	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
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 IL33 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	0.954	0.239
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.082	0.563
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.89	0.451
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.184	0.0629
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.866	0.485
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.59	0.25
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.305	0.623
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.11	0.944
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.843	0.608
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.095	0.377
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	1.851	0.292
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.676	0.00706

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL33 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL33. 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	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL33. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL33. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL33. 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	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL33 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL33 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL33
Name	interleukin 33
Aliases	DVS27; DKFZp586H0523; NF-HEV; IL1F11; DVS27-related protein; nuclear factor for high endothelial venules; in ......
Chromosomal Location	9p24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL33 collected from DrugBank database.

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

Browse IL33