TISIDB

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
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: Cytoplasm.
Domain	PF00020 TNFR/NGFR cysteine-rich region
Function	Receptor for TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002237 response to molecule of bacterial origin GO:0009612 response to mechanical stimulus GO:0032496 response to lipopolysaccharide GO:0032639 TRAIL production GO:0032640 tumor necrosis factor production GO:0032679 regulation of TRAIL production GO:0032680 regulation of tumor necrosis factor production GO:0032759 positive regulation of TRAIL production GO:0032760 positive regulation of tumor necrosis factor production GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034612 response to tumor necrosis factor GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042533 tumor necrosis factor biosynthetic process GO:0042534 regulation of tumor necrosis factor biosynthetic process GO:0042535 positive regulation of tumor necrosis factor biosynthetic process GO:0045553 TRAIL biosynthetic process GO:0045554 regulation of TRAIL biosynthetic process GO:0045556 positive regulation of TRAIL biosynthetic process 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:0071706 tumor necrosis factor superfamily cytokine production GO:1903555 regulation of tumor necrosis factor superfamily cytokine production GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
Molecular Function	GO:0005031 tumor necrosis factor-activated receptor activity GO:0005035 death receptor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-5669034: TNFs bind their physiological receptors

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TNFRSF8 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 TNFRSF8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18230757	Lymphoma	Immunotherapy target	Human antibody RNase fusion protein targeting CD30+ lymphomas. Targeted RNases (TRs) are immunoenzymes with ribonucleases as cytotoxic effector domains, which are less immunogenic as plant or bacterial toxin components of classical immunotoxins. Proliferation of the CD30+ lymphoma cell line Karpas-299 was strongly inhibited by CD30-specific huTR protein (IC50=3.3 nM).
19789316	Primary Cutaneous Anaplastic Large Cell Lymphoma; Lymphomatoid Papulosis	Essential for immunotherapy	The overall objective response rate [complete response (CR) + partial response (PR)] was 70% (16 of 23 patients): 10 patients achieved a CR and another 6 patients achieved a PR. Overall, clinical benefit of SGN-30, as assessed by achieving a response to therapy or stable disease (CR + PR + stable disease), was shown by 87% of patients during the study, including all patients with pc-ALCL or LyP and two thirds of patients with T-MF or with multiple clinical diagnoses. Nine of the 10 patients who achieved a CR and 5 of the 6 patients who achieved a PR were in remission at their follow-up evaluation (median duration, 84 days).
24916470	adenocarcinoma	Inhibit immunity (T cell function); decrease the efficacy of immunotherapy	Brentuximab vedotin represents a first-in-class ADC directed against CD30(+) malignancies.
23974006	Anaplastic Large Cell Lymphoma; Hodgkin Lymphoma	Inhibit immunity (T/NK cell function); immunotherapy target	Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer. CD30 is highly expressed on Hodgkins lymphoma and anaplastic large cell lymphoma, making it an attractive target for therapy. The multivalent aptamer was able to induce oligomerization of CD30 receptors and, in effect, activate downstream signaling, which led to apoptosis of ALCL cells.
28805662	Anaplastic Large Cell Lymphoma; Hodgkin Lymphoma	Inhibit immunity; Immunotherapy target	Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. CD30.CAR-Ts are safe and can lead to clinical responses in patients with HL and ALCL, indicating that further assessment of this therapy is warranted.
24395820	Melanoma	Inhibit immunity (T cell function)	Transcriptional profiling of melanoma sentinel nodes identify patients with poor outcome and reveal an association of CD30(+) T lymphocytes with progression. Phenotypic profiling demonstrated that CD30(+) lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4(+)Foxp3(+) or PD1(+) subpopulations and CD4(-)CD8(-) T cells.
17515574	Hodgkin Lymphoma	Inhibit immunity	Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1kappa monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models.

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
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 TNFRSF8 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	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
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 TNFRSF8 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	-0.675	0.099
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1	0.144
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.437	0.458
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.118	0.83
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.269	0.793
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.067	0.958
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.52	0.372
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.891	0.302
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.057	0.95
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.629	0.151
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	0.365	0.522
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.161	0.513

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TNFRSF8 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	6.8	-3.1	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	8.5	-4.8	0.66
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	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	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	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
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	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	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFRSF8. 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	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFRSF8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFRSF8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFRSF8. 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	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TNFRSF8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TNFRSF8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TNFRSF8
Name	tumor necrosis factor receptor superfamily, member 8
Aliases	KI-1; CD30; D1S166E; CD30L receptor; Ki-1 antigen; cytokine receptor CD30; lymphocyte activation antigen CD3 ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TNFRSF8 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TNFRSF8.

ID	Name	Drug Type	Targets	#Targets
DB08870	Brentuximab vedotin	Biotech	TNFRSF8	1

Browse TNFRSF8