TISIDB

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
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.
Domain	PF06083 Interleukin-17
Function	Ligand for IL17RA and IL17RC (PubMed:17911633). The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC (PubMed:18684971). Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines (PubMed:8676080).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002521 leukocyte differentiation GO:0002532 production of molecular mediator involved in inflammatory response GO:0002534 cytokine production involved in inflammatory response GO:0002573 myeloid leukocyte differentiation GO:0002761 regulation of myeloid leukocyte differentiation GO:0002763 positive regulation of myeloid leukocyte differentiation GO:0009306 protein secretion GO:0009620 response to fungus GO:0030099 myeloid cell differentiation GO:0030316 osteoclast differentiation GO:0031349 positive regulation of defense response GO:0032103 positive regulation of response to external stimulus GO:0032627 interleukin-23 production GO:0032635 interleukin-6 production GO:0032667 regulation of interleukin-23 production GO:0032675 regulation of interleukin-6 production GO:0032747 positive regulation of interleukin-23 production GO:0032755 positive regulation of interleukin-6 production GO:0045637 regulation of myeloid cell differentiation GO:0045639 positive regulation of myeloid cell differentiation GO:0045670 regulation of osteoclast differentiation GO:0045672 positive regulation of osteoclast differentiation 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:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050832 defense response to fungus GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0070555 response to interleukin-1 GO:0071347 cellular response to interleukin-1 GO:0072537 fibroblast activation GO:0072604 interleukin-6 secretion GO:0098542 defense response to other organism GO:1900015 regulation of cytokine production involved in inflammatory response GO:1900017 positive regulation of cytokine production involved in inflammatory response GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1903532 positive regulation of secretion by cell GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis GO:1904951 positive regulation of establishment of protein localization GO:2000778 positive regulation of interleukin-6 secretion
Molecular Function	GO:0005125 cytokine activity GO:0005126 cytokine receptor binding
Cellular Component	GO:0009897 external side of plasma membrane GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-448424: Interleukin-17 signaling R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-449147: Signaling by Interleukins

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IL17A 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 IL17A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26785144	Kidney Carcinoma	Promote immunity	These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer).
26719303	Colorectal Carcinoma	Promote immunity (infiltration)	Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release.
27620275	Gastric Carcinoma	Promote immunity (infiltration)	Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines.
24525743	Hepatocellular carcinoma	Inhibit immunity (T cell function); immunotherapy target	IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma. The tumor-promoting effect of IL-17A was mediated through suppression of antitumor responses, especially CD8(+) T-cell responses. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner. Conversely, IL-17A could also enhance production of IL-1β and IL-23 in MDSC as a positive feedback. These findings offer new insights into how IL-17A influences tumor immunity, with potential implications for the development of tumor immunotherapy.
23022528	Lung carcinoma	Promote immunity	As modulation of T cell cytokines such as IL-17A has been recently shown to suppress tumor growth in experimental models, anti-cytokine agents emerge as a promising new approach for treatment of lung cancer.
23420584	Malignant Splenic Neoplasm	Inhibit immunity (T cell function)	Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen.
19471017	Melanoma; Fibrosarcoma	Promote immunity	We skewed CD8(+) T cells to secrete IL-17 through priming in Th17-polarizing conditions. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells.
19470694	Ovarian Carcinoma	Promote immunity (infiltration)	Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome.
29604293	Pancreatic ductal adenocarcinoma; melanoma; colon carcinoma	Promote immunity	Immune cells that produce interleukin 17A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to pancreatic interepithelial neoplasia (PanIN) initiation and progression.
21455984	Other Mammary Carcinoma of Mouse	Inhibit immunity	TLR4 deficient mice developed more tumors relative to the WT mice. T cells of TLR4 deficient mice produced elevated levels of IL-17 and lower levels of IFN-γ relative to WT mice. IL-12 secreted by CD11c(+) cells was higher in WT mice, whereas greater amounts of IL-23 were produced by CD11c(+) cells from TLR4 deficient mice.
21300825	Metastatic Malignant Neoplasm in the Lung	Promote immunity (T cell function)	Reduced tumor progression along with improved T cell function was found in IL-17 KO mice, compared with WT mice.
22186896	Lung Adenocarcinoma	Promote immunity	Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-γ-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells.
21674477	Hepatocellular Carcinoma	Inhibit immunity (T cell function)	Interleukin-17-educated monocytes suppress cytotoxic T-cell function through B7-H1 in hepatocellular carcinoma patients. Accordingly, IL-17 could activate monocytes to express B7-H1 in a dose-dependent manner.Moreover, these IL-17-exposed monocytes effectively suppressed cytotoxic T-cell immunity in vitro; the effect could be reversed by blocking B7-H1 on those monocytes.

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
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 IL17A 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	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
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 IL17A 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	0.145	0.449
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.007	0.99
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.259	0.569
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.804	0.467
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.924	0.567
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.646	0.72
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	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.168	0.473

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IL17A 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	1.4	-1.4	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	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
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	0	9.1	-9.1	0.458
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	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IL17A. 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	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IL17A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IL17A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IL17A. 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	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IL17A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IL17A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IL17A
Name	interleukin 17A
Aliases	IL-17A; IL-17; cytotoxic T-lymphocyte-associated protein 8; CTLA8; IL17; interleukin 17 (cytotoxic T-lymphoc ......
Chromosomal Location	6p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IL17A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IL17A.

ID	Name	Drug Type	Targets	#Targets
DB09029	Secukinumab	Biotech	IL17A	1
DB11569	Ixekizumab	Biotech	IL17A	1

Browse IL17A