TISIDB

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
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	Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses.

> Gene Ontology [ TOP ]
Biological Process	GO:0002548 monocyte chemotaxis GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0031349 positive regulation of defense response GO:0032103 positive regulation of response to external stimulus GO:0034341 response to interferon-gamma GO:0034612 response to tumor necrosis factor GO:0043410 positive regulation of MAPK cascade GO:0048247 lymphocyte chemotaxis GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050900 leukocyte migration 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:0070555 response to interleukin-1 GO:0071346 cellular response to interferon-gamma GO:0071347 cellular response to interleukin-1 GO:0071356 cellular response to tumor necrosis factor GO:0071621 granulocyte chemotaxis GO:0071674 mononuclear cell migration GO:0072676 lymphocyte migration GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:1990266 neutrophil migration
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0008009 chemokine activity 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
Reactome	-

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCL18 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 CCL18 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28290464	Breast Carcinoma	Inhibit immunity (T cell function)	Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ.

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
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 CCL18 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	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
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 CCL18 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	-0.581	0.387
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.261	0.919
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.794	0.623
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.293	0.72
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.339	0.295
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.036	0.516
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.309	0.708
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.804	0.609
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.3	0.866
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	-0.033	0.912

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CCL18 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% 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	0	0	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	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	4.8	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	7.7	7.7	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	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCL18. 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	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCL18. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCL18. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCL18. 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	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCL18 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCL18 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCL18
Name	chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)
Aliases	DC-CK1; AMAC-1; DCCK1; MIP-4; CKb7; SCYA18; small inducible cytokine subfamily A (Cys-Cys), member 18, pulmo ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCL18 collected from DrugBank database.

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

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