TISIDB

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
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	PF00531 Death domain PF00020 TNFR/NGFR cysteine-rich region
Function	Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:10549288). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.

> Gene Ontology [ TOP ]
Biological Process	GO:0002237 response to molecule of bacterial origin GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007250 activation of NF-kappaB-inducing kinase activity GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0009612 response to mechanical stimulus GO:0010950 positive regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0032147 activation of protein kinase activity GO:0032496 response to lipopolysaccharide GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0033674 positive regulation of kinase activity GO:0034612 response to tumor necrosis factor GO:0034976 response to endoplasmic reticulum stress GO:0038061 NIK/NF-kappaB signaling GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0045860 positive regulation of protein kinase activity GO:0045862 positive regulation of proteolysis GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0071214 cellular response to abiotic stimulus GO:0071260 cellular response to mechanical stimulus GO:0071356 cellular response to tumor necrosis factor GO:0071496 cellular response to external stimulus GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0097191 extrinsic apoptotic signaling pathway GO:0097193 intrinsic apoptotic signaling pathway GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:1901222 regulation of NIK/NF-kappaB signaling GO:1901224 positive regulation of NIK/NF-kappaB signaling GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:2000116 regulation of cysteine-type endopeptidase activity GO:2001056 positive regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway GO:2001267 regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Molecular Function	GO:0005031 tumor necrosis factor-activated receptor activity GO:0005035 death receptor activity GO:0045569 TRAIL binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04115 p53 signaling pathway hsa04210 Apoptosis hsa04650 Natural killer cell mediated cytotoxicity
Reactome	R-HSA-109581: Apoptosis R-HSA-5218900: CASP8 activity is inhibited R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway R-HSA-202733: Cell surface interactions at the vascular wall R-HSA-73887: Death Receptor Signalling R-HSA-69416: Dimerization of procaspase-8 R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-109582: Hemostasis R-HSA-140534: Ligand-dependent caspase activation R-HSA-5357801: Programmed Cell Death R-HSA-5213460: RIPK1-mediated regulated necrosis R-HSA-5218859: Regulated Necrosis R-HSA-3371378: Regulation by c-FLIP R-HSA-5675482: Regulation of necroptotic cell death R-HSA-162582: Signal Transduction R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes R-HSA-6803211: TP53 Regulates Transcription of Death Receptors and Ligands R-HSA-75158: TRAIL signaling R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

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KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04115 p53 signaling pathway
hsa04210 Apoptosis
hsa04650 Natural killer cell mediated cytotoxicity

Reactome

R-HSA-109581: Apoptosis
R-HSA-5218900: CASP8 activity is inhibited
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-73887: Death Receptor Signalling
R-HSA-69416: Dimerization of procaspase-8
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-109582: Hemostasis
R-HSA-140534: Ligand-dependent caspase activation
R-HSA-5357801: Programmed Cell Death
R-HSA-5213460: RIPK1-mediated regulated necrosis
R-HSA-5218859: Regulated Necrosis
R-HSA-3371378: Regulation by c-FLIP
R-HSA-5675482: Regulation of necroptotic cell death
R-HSA-162582: Signal Transduction
R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes
R-HSA-6803211: TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-75158: TRAIL signaling
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TNFRSF10B 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 TNFRSF10B and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24639349	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Histone deacetylase inhibitor sensitizes apoptosis-resistant melanomas to cytotoxic human T lymphocytes through regulation of TRAIL/DR5 pathway. CTL resistance was due to DR5 downregulation and an inverted ratio of pro- to antiapoptotic molecules, both of which were reversed by the histone deacetylase inhibitor suberoylanilide hydroxanic acid.
16680149	Breast Carcinoma; Renal Cell Carcinoma; Colon Carcinoma; Lung Carcinoma	Promote immunity	Here we show that induction of tumor-cell apoptosis by an agonistic monoclonal antibody to DR5, the apoptosis-inducing receptor for TNF-related apoptosis-inducing ligand (TRAIL), combined with T-cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD40 and CD137, potently and rapidly stimulated tumor-specific effector CD8+ T cells capable of eradicating preestablished tumors. This combination therapy of three monoclonal antibodies (trimAb) rapidly induced tumor-specific CD8+ T cells producing interferon (IFN)-gamma in the tumor-draining lymph node, consistent with a crucial requirement for CD8+ T cells and IFN-gamma in the tumor rejection process.
22419388	Triple-Negative Breast Carcinoma	Immunotherapy target	Resulting immune serum or purified immune IgG induced apoptosis in triple-negative breast cancer (TNBC) cells, which were also TRAIL sensitive. Apoptotic cell death induced by anti-DR5 antibody was shown by the cleavage of PARP and caspase-3. In vivo, hDR5 reactive immune serum prevented growth of SUM159 TNBC cells in severe combined immune-deficient mice. These findings support DR5 as a promising vaccine target for controlling TNBC and other DR5-positive cancers.
19147771	Renal Cell Carcinoma	Inhibit immunity	The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R) are involved in immune surveillance and tumor development. High TRAIL-R2 expression levels were associated with high-grade RCCs (P < 0.001) and correlated negatively with disease-specific survival (P = 0.01). Similarly, high TRAIL expression was associated with a shorter disease-specific survival (P = 0.01).

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
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 TNFRSF10B 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	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
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 TNFRSF10B 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	-0.397	0.472
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.02	0.993
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.665	0.661
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.277	0.469
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.16	0.941
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.426	0.879
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.272	0.652
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.473	0.8
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.169	0.931
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.1	0.95
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	0.726	0.76
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.34	0.00157

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TNFRSF10B 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	2.7	-2.7	1
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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	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	0	0	0	1
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	0	3.7	-3.7	0.415
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	7.1	-7.1	0.467
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	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFRSF10B. 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	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFRSF10B. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFRSF10B. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFRSF10B. 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	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TNFRSF10B expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TNFRSF10B and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TNFRSF10B
Name	tumor necrosis factor receptor superfamily, member 10b
Aliases	DR5; KILLER; TRICK2A; TRAIL-R2; TRICKB; CD262; KILLER/DR5; TRAILR2; TRICK2; TRICK2B; ZTNFR9; Fas-like protei ......
Chromosomal Location	8p22-p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TNFRSF10B collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TNFRSF10B.

ID	Name	Drug Type	Targets	#Targets
DB05895	HGS-TR2J	Biotech	TNFRSF10B	1
DB06599	Lexatumumab	Biotech	TNFRSF10B	1

Browse TNFRSF10B