TISIDB

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
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; Multi-pass membrane protein.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response.

> Gene Ontology [ TOP ]
Biological Process	GO:0003012 muscle system process GO:0006936 muscle contraction GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007218 neuropeptide signaling pathway GO:0061737 leukotriene signaling pathway
Molecular Function	GO:0001632 leukotriene B4 receptor activity GO:0001653 peptide receptor activity GO:0004953 icosanoid receptor activity GO:0004974 leukotriene receptor activity GO:0008528 G-protein coupled peptide receptor activity
Cellular Component	GO:0045121 membrane raft GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04080 Neuroactive ligand-receptor interaction
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-391903: Eicosanoid ligand-binding receptors R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-391906: Leukotriene receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between LTB4R 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 LTB4R and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27465528	Melanoma	Promote immunity (infiltration)	Significant accelerations in tumor growth and reduced survival were observed in both BLT1(-/-) and CXCR3(-/-) mice as compared with wild-type (WT) mice. The loss of efficacy correlated with failure of the knockout CTLs to infiltrate into tumors upon anti-PD-1 treatment, suggesting an obligate requirement for both BLT1 and CXCR3 in mediating anti-PD-1 based antitumor immune response. These results demonstrate a critical role for both BLT1 and CXCR3 in CTL migration to tumors and thus may be targeted to enhance efficacy of CTL-based immunotherapies.
23960231	Cervical Carcinoma	Promote immunity (infiltration)	Expression of leukotriene B? receptor-1 on CD8? T cells is required for their migration into tumors to elicit effective antitumor immunity. In this study, we investigated the role of BLT1 in antitumor immunity using syngeneic TC-1 cervical cancer model, and observed accelerated tumor growth and reduced survival in BLT1?/? mice compared with BLT1?/? mice. Gene expression profiling confirmed the dramatic decrease of IFN-γ, granzyme B, and IL-2 in tumors growing in BLT1?/? mice. Furthermore, depletion of CD8? T cells enhanced the tumor growth in BLT1?/? but not in BLT1?/? mice. These results suggest that BLT1 expression on CD8? T cells plays an important role in their trafficking to tumors.
22936657	Mouse Myelomonocytic Leukemia	Promote immunity	Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF-induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems. We here demonstrated that BLT1-deficient mice rejected subcutaneous tumor challenge of GM-CSF gene-transduced WEHI3B (WGM) leukemia cells (KO/WGM) and elicited robust antitumor responses against second tumor challenge with WEHI3B cells. During GM-CSF-induced tumor regression, the defective LTB4/BLT1 signaling significantly reduced tumor-infiltrating myeloid-derived suppressor cells, increased the maturation status of dendritic cells in tumor tissues, enhanced their CD4(+) T-cell stimulation capacity and migration rate of dendritic cells that had phagocytosed tumor-associated antigens into tumor-draining lymph nodes, suggesting a positive impact on GM-CSF-sensitized innate immunity.

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
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 LTB4R 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	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
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 LTB4R 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	0.347	0.475
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.387	0.715
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.885	0.282
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.393	0.346
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.331	0.825
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.478	0.815
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.046	0.906
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.247	0.824
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.112	0.922
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.243	0.806
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	0.085	0.949
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.192	0.132

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of LTB4R 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	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	0	0	1
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	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LTB4R. 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	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LTB4R. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LTB4R. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LTB4R. 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	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LTB4R expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LTB4R and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LTB4R
Name	leukotriene B4 receptor
Aliases	BLTR; P2Y7; LTB4R1; P2RY7; GPR16; CMKRL1; BLT1; LTBR1; G protein-coupled receptor 16; G-protein coupled rece ......
Chromosomal Location	14q11.2-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LTB4R collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting LTB4R.

ID	Name	Drug Type	Targets	#Targets
DB06248	Amelubant	Small Molecule	LTB4R, LTB4R2	2
DB09285	Morniflumate	Small Molecule	ALOX5, LTB4R, PTGS2, TBXA2R	4
DB12961	Leukotriene B4	Small Molecule	LTB4R, LTB4R2, PPARA	3

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