TISIDB

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
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	Isoform 1: Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Isoform 2: Secreted.; SUBCELLULAR LOCATION: Tumor necrosis factor-binding protein 2: Secreted.
Domain	PF00020 TNFR/NGFR cysteine-rich region
Function	Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0002237 response to molecule of bacterial origin GO:0006509 membrane protein ectodomain proteolysis GO:0007568 aging GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010608 posttranscriptional regulation of gene expression GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0031348 negative regulation of defense response GO:0032102 negative regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0033619 membrane protein proteolysis GO:0034612 response to tumor necrosis factor GO:0042176 regulation of protein catabolic process GO:0043410 positive regulation of MAPK cascade GO:0043487 regulation of RNA stability GO:0045732 positive regulation of protein catabolic process GO:0045862 positive regulation of proteolysis GO:0050727 regulation of inflammatory response GO:0050728 negative regulation of inflammatory response GO:0050779 RNA destabilization GO:0051043 regulation of membrane protein ectodomain proteolysis GO:0051044 positive regulation of membrane protein ectodomain proteolysis GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071356 cellular response to tumor necrosis factor GO:0071396 cellular response to lipid GO:0097191 extrinsic apoptotic signaling pathway GO:0097193 intrinsic apoptotic signaling pathway
Molecular Function	GO:0005031 tumor necrosis factor-activated receptor activity GO:0005035 death receptor activity GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding
Cellular Component	GO:0030424 axon GO:0033267 axon part GO:0043025 neuronal cell body GO:0043196 varicosity GO:0044297 cell body GO:0044304 main axon GO:0045121 membrane raft GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04668 TNF signaling pathway hsa04920 Adipocytokine signaling pathway
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6783783: Interleukin-10 signaling R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-6798695: Neutrophil degranulation R-HSA-449147: Signaling by Interleukins R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-5669034: TNFs bind their physiological receptors

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TNFRSF1B 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 TNFRSF1B and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26483205	Colon Carcinoma; Lung Carcinoma	Inhibit immunity (T cell function)	Overall, our findings implicate TNFR2 in supporting MDSC-mediated immune suppression and metastasis in the liver, suggesting the use of TNFR2 inhibitors as a strategy to prevent metastatic progression to liver in colon, lung, and various other types of cancer.
26896171	Melanoma	Inhibit immunity (T cell function)	In sharp contrast, DN-TNF treatment dramatically decreased IL1α and increased the essential immunoregulatory cytokines IL1β, IL12p70, and IL17 in the peripheral blood of MCA-injected mice. In addition, MDSC accumulation, STAT3 phosphorylation, and immunosuppression in MCA-injected mice were prevented by DN-TNF treatment, TNFR2-Fc treatment, and/or gene deletion of TNF or TNFR1, but not deletion of TNFR2.
29295954	Colon carcinoma	Inhibit immunity (T/NK cell function); immunotherapy target	Those Treg cells that have a high abundance of TNFR2 have the maximal immunosuppressive capacity. We investigated whether targeting TNFR2 could effectively suppress the activity of Treg cells and consequently enhance the efficacy of cancer immunotherapy.
18453563	Lung Carcinoma	Inhibit immunity	Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells. In the Lewis lung carcinoma model, more highly suppressive TNFR2(+) Tregs accumulated intratumorally than in the periphery. Thus, TNFR2 identifies a unique subset of mouse Tregs with an activated/memory phenotype and maximal suppressive activity that may account for tumor-infiltrating lymphocyte-mediated immune evasion by tumors.
29632537	ovarian carcinoma	Inhibit immunity (T cell function); immunotherapy target	These studies clearly show that TNFR2-targeting pharmacological agents represent an effective approach to modulating the function of Tregs and thus may be useful in the treatment of major human diseases such as autoimmune disorders, graft-versus-host disease (GVHD), and cancer.
24379122	Breast Carcinoma	Inhibit immunity	Transmembrane TNF-α promotes suppressive activities of myeloid-derived suppressor cells via TNFR2. This effect of tmTNF-α was mediated by TNFR2, as TNFR2 deficiency significantly impaired tmTNF-α-induced release of IL-10 and NO and inhibition of T cell proliferation by MDSC supernatant.
24297862	Acute Myeloid Leukemia	Inhibit immunity	We report that TNFR2(+) Tregs are increased in AML and have a high migration potential toward the bone marrow. Reductions in TNFR2(+) Tregs were associated with increases in Interferon (IFN)-γ and interleukin (IL)-2 production by effector T cells within the bone marrow and beneficial clinical responses.
20525892	Breast Neoplasm; Lung Carcinoma	Inhibit immunity (expressed by Tregs); Promote immunity (expressed by Tconv)	TNFR2 is associated with greater suppressive functions when expressed by Tregs and is associated with greater resistance to suppression when expressed by Tconv cells. In mice bearing 4T1 breast tumor or Lewis lung carcinoma, intratumoral Tconv cells expressing elevated levels of TNFR2 acquired the capacity to resist suppression by lymph node-derived Tregs. However, intratumoral Tregs expressing more TNFR2 are able to overcome the greater resistance to suppression of intratumoral Tconv cells, resulting in a dominant immunosuppressive tumor environment.

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
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 TNFRSF1B 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	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
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 TNFRSF1B 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	-0.534	0.15
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.461	0.816
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.585	0.682
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.078	0.861
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.494	0.791
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.453	0.857
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.311	0.534
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.591	0.702
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.034	0.984
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.483	0.348
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	1.496	0.541
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.164	0.264

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TNFRSF1B 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	4.8	5.9	-1.1	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	7.7	9.1	-1.4	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	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFRSF1B. 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	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFRSF1B. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFRSF1B. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFRSF1B. 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	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TNFRSF1B expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TNFRSF1B and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TNFRSF1B
Name	tumor necrosis factor receptor superfamily, member 1B
Aliases	TNFBR; TNFR80; TNF-R75; TNF-R-II; CD120b; TNFR2; TBPII; TNFR1B; p75TNFR; TNF-R2; TNF-RII; p75 TNF receptor; ......
Chromosomal Location	1p36.22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TNFRSF1B collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TNFRSF1B.

ID	Name	Drug Type	Targets	#Targets
DB00005	Etanercept	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	14
DB11626	Tasonermin	Biotech	TNFRSF1A, TNFRSF1B	2

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