TISIDB

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
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=The lack of a specific hydrophobic segment in the precursor sequence suggests that IL-1 is released by damaged cells or is secreted by a mechanism differing from that used for other secretory proteins.
Domain	PF00340 Interleukin-1 / 18 PF02394 Interleukin-1 propeptide
Function	Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001659 temperature homeostasis GO:0001660 fever generation GO:0001819 positive regulation of cytokine production GO:0002246 wound healing involved in inflammatory response GO:0002248 connective tissue replacement involved in inflammatory response wound healing GO:0002526 acute inflammatory response GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002691 regulation of cellular extravasation GO:0002693 positive regulation of cellular extravasation GO:0006953 acute-phase response GO:0007067 mitotic nuclear division GO:0007088 regulation of mitotic nuclear division GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007254 JNK cascade GO:0007346 regulation of mitotic cell cycle GO:0009266 response to temperature stimulus GO:0009306 protein secretion GO:0009408 response to heat GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010573 vascular endothelial growth factor production GO:0010574 regulation of vascular endothelial growth factor production GO:0010575 positive regulation of vascular endothelial growth factor production GO:0010623 programmed cell death involved in cell development GO:0030335 positive regulation of cell migration GO:0031098 stress-activated protein kinase signaling cascade GO:0031649 heat generation GO:0032602 chemokine production GO:0032623 interleukin-2 production GO:0032635 interleukin-6 production GO:0032642 regulation of chemokine production GO:0032663 regulation of interleukin-2 production GO:0032675 regulation of interleukin-6 production GO:0032722 positive regulation of chemokine production GO:0032743 positive regulation of interleukin-2 production GO:0032755 positive regulation of interleukin-6 production GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0034605 cellular response to heat GO:0035234 ectopic germ cell programmed cell death GO:0038034 signal transduction in absence of ligand GO:0040017 positive regulation of locomotion GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042094 interleukin-2 biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043410 positive regulation of MAPK cascade GO:0045076 regulation of interleukin-2 biosynthetic process GO:0045086 positive regulation of interleukin-2 biosynthetic process GO:0045123 cellular extravasation GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045787 positive regulation of cell cycle GO:0045840 positive regulation of mitotic nuclear division GO:0045931 positive regulation of mitotic cell cycle GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0046688 response to copper ion GO:0048514 blood vessel morphogenesis GO:0048771 tissue remodeling GO:0048871 multicellular organismal homeostasis GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050715 positive regulation of cytokine secretion GO:0050900 leukocyte migration GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051272 positive regulation of cellular component movement GO:0051302 regulation of cell division GO:0051403 stress-activated MAPK cascade GO:0051781 positive regulation of cell division GO:0051783 regulation of nuclear division GO:0051785 positive regulation of nuclear division GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0070498 interleukin-1-mediated signaling pathway GO:0070555 response to interleukin-1 GO:0071347 cellular response to interleukin-1 GO:0071605 monocyte chemotactic protein-1 production GO:0071637 regulation of monocyte chemotactic protein-1 production GO:0071639 positive regulation of monocyte chemotactic protein-1 production GO:0072672 neutrophil extravasation GO:0090068 positive regulation of cell cycle process GO:0090594 inflammatory response to wounding GO:0097191 extrinsic apoptotic signaling pathway GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:0097709 connective tissue replacement GO:1901099 negative regulation of signal transduction in absence of ligand GO:1901342 regulation of vasculature development GO:1902622 regulation of neutrophil migration GO:1902624 positive regulation of neutrophil migration GO:1903532 positive regulation of secretion by cell GO:1904018 positive regulation of vasculature development GO:1904951 positive regulation of establishment of protein localization GO:1990266 neutrophil migration GO:1990267 response to transition metal nanoparticle GO:2000147 positive regulation of cell motility GO:2000389 regulation of neutrophil extravasation GO:2000391 positive regulation of neutrophil extravasation GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function	GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005149 interleukin-1 receptor binding GO:0005507 copper ion binding GO:0070851 growth factor receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04060 Cytokine-cytokine receptor interaction hsa04380 Osteoclast differentiation hsa04640 Hematopoietic cell lineage
Reactome	R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-448706: Interleukin-1 processing R-HSA-446652: Interleukin-1 signaling R-HSA-6783783: Interleukin-10 signaling R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP) R-HSA-449147: Signaling by Interleukins

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04010 MAPK signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04380 Osteoclast differentiation
hsa04640 Hematopoietic cell lineage

Reactome

R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-448706: Interleukin-1 processing
R-HSA-446652: Interleukin-1 signaling
R-HSA-6783783: Interleukin-10 signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-449147: Signaling by Interleukins

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL1A 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 IL1A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18412246	Fibrosarcoma	Promote immunity	Opposing effects of fibrosarcoma cell-derived IL-1 alpha and IL-1 beta on immune response induction. Induction of a strong immune response by IL-1 alpha demands therapeutic exploitation, which may become more efficient if systemic induction of immunosuppression by IL-1 beta can also be circumvented.
21300825	Metastatic Malignant Neoplasm in the Lung	Promote immunity (T cell function)	The absence of IL-1 signaling or its excess in the lung microenvironment (in IL-1β and IL-1R antagonist knockout [KO] mice, respectively) resulted in a poor prognosis and reduced T cell activity, compared with WT mice. In IL-1β KO mice, enhanced T regulatory cell development/function, due to a favorable in situ cytokine network and impairment in APC maturation, resulted in suppressed antitumor immunity, whereas in IL-1R antagonist KO mice, enhanced accumulation and activity of myeloid-derived suppressor cells were found. In the microenvironment of lung tumors, IL-1 induces IL-17 through recruitment of γ/δ T cells and their activation for IL-17 production, with no involvement of Th17 cells.
20099279	Melanoma	Inhibit immunity (T cell function)	Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.
22850568	Melanoma	Inhibit immunity	Treatment of melanoma-patient-derived TAFs with IL-1α/β significantly enhanced their ability to suppress the proliferation and function of melanoma-specific cytotoxic T cells, and this inhibition was partially attributable to upregulation by IL-1 of COX-2 and the PD-1 ligands PD-L1 and PD-L2 in TAFs.

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
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 IL1A 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	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
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 IL1A 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	-0.063	0.852
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.395	0.503
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.186	0.727
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.935	0.101
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.023	0.449
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.819	0.637
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.282	0.701
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.034	0.976
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.808	0.545
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.004	0.992
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	-0.192	0.729
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.455	0.145

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL1A 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	0	0	0	1
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	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL1A. 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	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL1A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL1A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL1A. 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	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL1A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL1A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL1A
Name	interleukin 1, alpha
Aliases	IL1F1; IL-1A; IL1-ALPHA; preinterleukin 1 alpha; hematopoietin-1; pro-interleukin-1-alpha; IL1; IL-1 alpha; ......
Chromosomal Location	2q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL1A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IL1A.

ID	Name	Drug Type	Targets	#Targets
DB06372	Rilonacept	Biotech	IL1A, IL1B, IL1RN	3

Browse IL1A