TISIDB

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
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	Membrane Single-pass type I membrane protein
Domain	PF13855 Leucine rich repeat PF01582 TIR domain
Function	Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.

> Gene Ontology [ TOP ]
Biological Process	GO:0001774 microglial cell activation GO:0001819 positive regulation of cytokine production GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002250 adaptive immune response GO:0002274 myeloid leukocyte activation GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0009306 protein secretion GO:0009612 response to mechanical stimulus GO:0009615 response to virus GO:0016064 immunoglobulin mediated immune response GO:0019724 B cell mediated immunity GO:0031349 positive regulation of defense response GO:0032479 regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032606 type I interferon production GO:0032607 interferon-alpha production GO:0032608 interferon-beta production GO:0032609 interferon-gamma production GO:0032637 interleukin-8 production GO:0032647 regulation of interferon-alpha production GO:0032648 regulation of interferon-beta production GO:0032649 regulation of interferon-gamma production GO:0032677 regulation of interleukin-8 production GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0032729 positive regulation of interferon-gamma production GO:0032757 positive regulation of interleukin-8 production GO:0034158 toll-like receptor 8 signaling pathway GO:0034162 toll-like receptor 9 signaling pathway GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042095 interferon-gamma biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042116 macrophage activation GO:0042228 interleukin-8 biosynthetic process GO:0045072 regulation of interferon-gamma biosynthetic process GO:0045078 positive regulation of interferon-gamma biosynthetic process GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045349 interferon-alpha biosynthetic process GO:0045350 interferon-beta biosynthetic process GO:0045351 type I interferon biosynthetic process GO:0045354 regulation of interferon-alpha biosynthetic process GO:0045356 positive regulation of interferon-alpha biosynthetic process GO:0045357 regulation of interferon-beta biosynthetic process GO:0045359 positive regulation of interferon-beta biosynthetic process GO:0045414 regulation of interleukin-8 biosynthetic process GO:0045416 positive regulation of interleukin-8 biosynthetic process GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0051607 defense response to virus GO:0071214 cellular response to abiotic stimulus GO:0071260 cellular response to mechanical stimulus GO:0071496 cellular response to external stimulus GO:0098542 defense response to other organism
Molecular Function	GO:0003725 double-stranded RNA binding GO:0003727 single-stranded RNA binding GO:0008144 drug binding
Cellular Component	GO:0005765 lysosomal membrane GO:0010008 endosome membrane GO:0036019 endolysosome GO:0036020 endolysosome membrane GO:0044440 endosomal part GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04620 Toll-like receptor signaling pathway
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade R-HSA-168898: Toll-Like Receptors Cascades R-HSA-1679131: Trafficking and processing of endosomal TLR

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04620 Toll-like receptor signaling pathway

Reactome

R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-1679131: Trafficking and processing of endosomal TLR

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TLR8 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

[ TOP ]

Literatures describing the relation between TLR8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25825448	Non-Small Cell Lung Carcinoma	Promote immunity (T cell function)	The ability of TLR7/8 agonists to reverse mMDSC-mediated immune suppression suggests that they might be useful adjuncts for tumor immunotherapy.
28453702	Ovarian Seromucinous Carcinoma	Promote immunity	A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.
18056169	Prostate Carcinoma	Promote immunity (T cell function)	Importantly, the suppressive function of CD8(+) Treg cells could be reversed by human Toll-like receptor 8 (TLR8) signaling.
23995793	Skin Basal Cell Carcinoma	Promote immunity (T cell function)	It is reported to be a TLR7 and TLR8 agonist and, as such, initiates a Th1 immune response by activating sentinel cells in the vicinity of the tumour.
20237413	Lung Carcinoma	Inhibit immunity	Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. Stimulation with TLR7 or TLR8 agonists led to activated NF-kappaB, upregulated expression of the antiapoptotic protein Bcl-2, increased tumor cell survival, and chemoresistance.
17535975	Skin Basal Cell Carcinoma	Promote immunity	Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. The biological relevance of this observation can be deduced from our further findings that peripheral blood-derived CD11c(+) mDCs acquired antiperforin and anti-granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class I(lo) cancer cell lines.
25231413	melanoma; breast carcinoma; ovarian carcinoma; colon carcinoma	Promote immunity (T cell function)	Importantly, activation of TLR8 signaling in tumor cells can block the induction and reverse the suppression of senescent naive and tumor-specific T cells in vitro and in vivo, resulting in enhanced anti-tumor immunity.
23355732	Breast Carcinoma	Promote immunity	We found that gammadelta Treg cells induced immunosenescence in the targeted naive and effector T cells, as well as dendritic cells (DCs). Furthermore, senescent T cells and DCs induced by gammadelta Treg cells had altered phenotypes and impaired functions and developed potent suppressive activities, further amplifying the immunosuppression mediated by gammadelta Treg cells.

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
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

[ TOP ]

Statistical results of TLR8 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	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
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

[ TOP ]

Points in the above scatter plot represent the expression difference of TLR8 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	-0.109	0.796
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.061	0.938
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.141	0.825
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.424	0.439
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.072	0.392
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.396	0.8
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.788	0.219
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.533	0.204
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.001	0.999
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.129	0.132
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	1.227	0.299
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.054	0.804

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TLR8 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	3.7	4.1	-0.4	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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TLR8. 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	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TLR8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TLR8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TLR8. 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	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TLR8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TLR8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TLR8
Name	toll-like receptor 8
Aliases	CD288; CD antigen CD288
Chromosomal Location	Xp22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TLR8 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting TLR8.

ID	Name	Drug Type	Targets	#Targets
DB00724	Imiquimod	Small Molecule	TLR7, TLR8	2
DB06530	Resiquimod	Small Molecule	TLR7, TLR8	2

Browse TLR8