TISIDB

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
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	Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Processed fractalkine: Secreted
Domain	PF00048 Small cytokines (intecrine/chemokine)
Function	Acts as a ligand for both CX3CR1 and integrins. Binds to CX3CR1 (PubMed:23125415, PubMed:9931005, PubMed:21829356). Binds to integrins ITGAV:ITGB3 and ITGA4:ITGB1. Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner. In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins. In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 (PubMed:23125415, PubMed:24789099). The soluble form is chemotactic for T-cells and monocytes and not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium (PubMed:9024663, PubMed:9177350).

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001819 positive regulation of cytokine production GO:0002523 leukocyte migration involved in inflammatory response GO:0002548 monocyte chemotaxis GO:0016338 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0030336 negative regulation of cell migration 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:0032905 transforming growth factor beta1 production GO:0032908 regulation of transforming growth factor beta1 production GO:0032914 positive regulation of transforming growth factor beta1 production GO:0033622 integrin activation GO:0034341 response to interferon-gamma GO:0034612 response to tumor necrosis factor GO:0038034 signal transduction in absence of ligand GO:0040013 negative regulation of locomotion GO:0043410 positive regulation of MAPK cascade GO:0045123 cellular extravasation GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045785 positive regulation of cell adhesion GO:0048246 macrophage chemotaxis GO:0048247 lymphocyte chemotaxis GO:0048514 blood vessel morphogenesis GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050900 leukocyte migration GO:0050902 leukocyte adhesive activation GO:0051040 regulation of calcium-independent cell-cell adhesion GO:0051041 positive regulation of calcium-independent cell-cell adhesion GO:0051271 negative regulation of cellular component movement GO:0060055 angiogenesis involved in wound healing 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:0071604 transforming growth factor beta production GO:0071621 granulocyte chemotaxis GO:0071634 regulation of transforming growth factor beta production GO:0071636 positive regulation of transforming growth factor beta production GO:0071674 mononuclear cell migration GO:0072676 lymphocyte migration 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:0098742 cell-cell adhesion via plasma-membrane adhesion molecules GO:1901099 negative regulation of signal transduction in absence of ligand GO:1901342 regulation of vasculature development GO:1904018 positive regulation of vasculature development GO:1990266 neutrophil migration GO:2000146 negative regulation of cell motility 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:0001664 G-protein coupled receptor binding GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005178 integrin binding GO:0008009 chemokine activity GO:0031737 CX3C chemokine receptor binding GO:0042379 chemokine receptor binding GO:0048020 CCR chemokine receptor binding GO:0050839 cell adhesion molecule 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-500792: GPCR ligand binding R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CX3CL1 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 CX3CL1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25428504	Melanoma	Inhibit immunity (T cell function); resistant to immunotherapy	Furthermore, responses were associated with T-helper type 1 (TH1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens.
17372897	B16 Malignant Melanoma	Promote immunity	We found that B16-treated CX3CR1-/- mice had increased lung tumor burden and cachexia. However, CX3CR1-deficient NK cells exhibited a tumorigenic cytokine production profile with defective IFN-gamma expression and enhanced IL-6 production in response to TLR3 activation with polyIC. Our studies indicate that CX3CR1 is an important contributor to innate immunity at multiple levels.
17332365	Neuroblastoma	Promote immunity	Therefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2-enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines.

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
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 CX3CL1 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	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
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 CX3CL1 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	0.744	0.153
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.713	0.702
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.773	0.564
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.365	0.549
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.671	0.695
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.02	0.993
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.101	0.824
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.104	0.93
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.159	0.907
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.839	0.668
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	0.844	0.765
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.248	0.194

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CX3CL1 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	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	0	3.7	0.314
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	16.7	-16.7	0.429
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	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CX3CL1. 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	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CX3CL1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CX3CL1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CX3CL1. 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	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CX3CL1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CX3CL1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CX3CL1
Name	chemokine (C-X3-C motif) ligand 1
Aliases	C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location	16q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CX3CL1 collected from DrugBank database.

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

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