TISIDB

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
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	PF00048 Small cytokines (intecrine/chemokine)
Function	Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:11352563, PubMed:11035086, PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases (PubMed:21376174). CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes (PubMed:9038201, PubMed:11352563). Involved in the recruitment of both the proinflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells (By similarity). C-terminal processed forms have been shown to be equally chemotactically active for leukocytes (PubMed:11035086). Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility (PubMed:23765988, PubMed:25122636). Inhibits proliferation of myeloid progenitors in colony formation assays (PubMed:9129037). May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells (By similarity). Possesses antibacterial activity towards E.coli ATCC 25922 and S.aureus ATCC 29213 (PubMed:12149255).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002237 response to molecule of bacterial origin GO:0002548 monocyte chemotaxis GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0030335 positive regulation of cell migration GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0032496 response to lipopolysaccharide GO:0032610 interleukin-1 alpha production GO:0032612 interleukin-1 production GO:0032650 regulation of interleukin-1 alpha production GO:0032652 regulation of interleukin-1 production GO:0032730 positive regulation of interleukin-1 alpha production GO:0032732 positive regulation of interleukin-1 production GO:0034341 response to interferon-gamma GO:0034612 response to tumor necrosis factor GO:0035584 calcium-mediated signaling using intracellular calcium source GO:0040017 positive regulation of locomotion GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042222 interleukin-1 biosynthetic process GO:0042742 defense response to bacterium GO:0043410 positive regulation of MAPK cascade GO:0045360 regulation of interleukin-1 biosynthetic process GO:0045362 positive regulation of interleukin-1 biosynthetic process GO:0048247 lymphocyte chemotaxis GO:0050719 interleukin-1 alpha biosynthetic process GO:0050721 regulation of interleukin-1 alpha biosynthetic process GO:0050726 positive regulation of interleukin-1 alpha biosynthetic process GO:0050900 leukocyte migration GO:0051272 positive regulation of cellular component movement GO:0051767 nitric-oxide synthase biosynthetic process GO:0051769 regulation of nitric-oxide synthase biosynthetic process GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process GO:0060326 cell chemotaxis GO:0070098 chemokine-mediated signaling pathway GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0070391 response to lipoteichoic acid GO:0070555 response to interleukin-1 GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071223 cellular response to lipoteichoic acid GO:0071346 cellular response to interferon-gamma GO:0071347 cellular response to interleukin-1 GO:0071356 cellular response to tumor necrosis factor GO:0071396 cellular response to lipid GO:0071621 granulocyte chemotaxis GO:0071674 mononuclear cell migration GO:0072676 lymphocyte migration GO:0072678 T cell migration GO:0072679 thymocyte migration GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:0098542 defense response to other organism GO:1990266 neutrophil migration GO:2000147 positive regulation of cell motility GO:2000401 regulation of lymphocyte migration GO:2000403 positive regulation of lymphocyte migration GO:2000404 regulation of T cell migration GO:2000406 positive regulation of T cell migration
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0008009 chemokine activity GO:0031731 CCR6 chemokine receptor binding GO:0042379 chemokine receptor binding GO:0048020 CCR chemokine receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway hsa04668 TNF signaling pathway
Reactome	R-HSA-380108: Chemokine receptors bind chemokines R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-168256: Immune System R-HSA-6783783: Interleukin-10 signaling R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-449147: Signaling by Interleukins

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04668 TNF signaling pathway

Reactome

R-HSA-380108: Chemokine receptors bind chemokines
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-449147: Signaling by Interleukins

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCL20 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 CCL20 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
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.
26837767	Hepatocellular Carcinoma	Inhibit immunity (T cell function)	Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.
25505237	Nasopharyngeal Carcinoma	Inhibit immunity (T cell function)	CCL20 allowed the intratumoral recruitment of human Treg.
16709808	Melanoma	Promote immunity	Our studies suggest that CCL20 processing in the extracellular environment of melanoma cells is exclusively mediated by cathepsin D. Thus, we propose a model where cathepsin D inactivates CCL20 and possibly prevents the establishment of an effective antitumoral immune response in melanomas.
27530322	Glioblastoma	Inhibit immunity (T cell function)	CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T Cells and Myeloid-Derived Suppressor Cells. In many aggressive cancers, such as glioblastoma multiforme, progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). Here we report that macrophages and microglia within the glioma microenvironment produce CCL2, a chemokine that is critical for recruiting both CCR4+?Treg and CCR2+Ly-6C+?monocytic MDSCs in this disease setting. In murine gliomas, we established novel roles for tumor-derived CCL20 and osteoprotegerin in inducing CCL2 production from macrophages and microglia.
18684866	Hodgkin Lymphoma	Inhibit immunity (T cell function)	Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3alpha (MIP-3alpha) in HRS cells. MIP-3alpha in turn attracts CCR6(+)CD4(+)CD25(+)FoxP3(+)CD127(lo) regulatory T cells toward HRS cells, which might favor their immune escape.

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
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 CCL20 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	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
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 CCL20 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	0.175	0.793
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.229	0.841
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.124	0.905
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.328	0.165
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.934	0.0355
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.724	0.633
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.998	0.212
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.25	0.829
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.937	0.118
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.682	0.738
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	1.378	0.623
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.243	0.455

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CCL20 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	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
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	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCL20. 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	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCL20. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCL20. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCL20. 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	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCL20 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCL20 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCL20
Name	chemokine (C-C motif) ligand 20
Aliases	LARC; MIP-3a; exodus-1; ST38; CKb4; SCYA20; small inducible cytokine subfamily A (Cys-Cys), member 20; Exodu ......
Chromosomal Location	2q36.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCL20 collected from DrugBank database.

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

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