TISIDB

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
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	Nucleus. Cytoplasm. Note=The phosphorylated and active form accumulates selectively in the nucleus.
Domain	PF00605 Interferon regulatory factor transcription factor PF10401 Interferon-regulatory factor 3
Function	Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0001959 regulation of cytokine-mediated signaling pathway GO:0001961 positive regulation of cytokine-mediated signaling pathway 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: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:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002753 cytoplasmic pattern recognition receptor signaling pathway GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002756 MyD88-independent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002761 regulation of myeloid leukocyte differentiation GO:0002764 immune response-regulating signaling pathway GO:0002819 regulation of adaptive immune response GO:0006925 inflammatory cell apoptotic process GO:0009615 response to virus GO:0016064 immunoglobulin mediated immune response GO:0019042 viral latency GO:0019043 establishment of viral latency GO:0019724 B cell mediated immunity GO:0030099 myeloid cell differentiation GO:0030224 monocyte differentiation GO:0030522 intracellular receptor signaling pathway 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:0032647 regulation of interferon-alpha production GO:0032648 regulation of interferon-beta production GO:0032727 positive regulation of interferon-alpha production GO:0032728 positive regulation of interferon-beta production GO:0033028 myeloid cell apoptotic process GO:0033032 regulation of myeloid cell apoptotic process GO:0033033 negative regulation of myeloid cell apoptotic process GO:0034121 regulation of toll-like receptor signaling pathway GO:0034124 regulation of MyD88-dependent toll-like receptor signaling pathway GO:0034127 regulation of MyD88-independent toll-like receptor signaling pathway GO:0034340 response to type I interferon GO:0034341 response to interferon-gamma GO:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039530 MDA-5 signaling pathway GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045351 type I interferon biosynthetic process GO:0045637 regulation of myeloid cell differentiation GO:0045655 regulation of monocyte differentiation GO:0051607 defense response to virus GO:0060333 interferon-gamma-mediated signaling pathway GO:0060337 type I interferon signaling pathway GO:0060338 regulation of type I interferon-mediated signaling pathway GO:0060340 positive regulation of type I interferon-mediated signaling pathway GO:0060759 regulation of response to cytokine stimulus GO:0060760 positive regulation of response to cytokine stimulus GO:0071346 cellular response to interferon-gamma GO:0071357 cellular response to type I interferon GO:0071887 leukocyte apoptotic process GO:0071888 macrophage apoptotic process GO:0098542 defense response to other organism GO:0098586 cellular response to virus GO:1902105 regulation of leukocyte differentiation GO:1903131 mononuclear cell differentiation GO:1903706 regulation of hemopoiesis GO:2000106 regulation of leukocyte apoptotic process GO:2000107 negative regulation of leukocyte apoptotic process GO:2000109 regulation of macrophage apoptotic process GO:2000110 negative regulation of macrophage apoptotic process
Molecular Function	GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding
Cellular Component	GO:0010008 endosome membrane GO:0044440 endosomal part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04622 RIG-I-like receptor signaling pathway hsa04623 Cytosolic DNA-sensing pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA R-HSA-3134963: DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-HSA-983231: Factors involved in megakaryocyte development and platelet production R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-877300: Interferon gamma signaling R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-918233: TRAF3-dependent IRF activation pathway R-HSA-933541: TRAF6 mediated IRF7 activation R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade 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

> KEGG and Reactome Pathway

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KEGG

hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04623 Cytosolic DNA-sensing pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-3134963: DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-983231: Factors involved in megakaryocyte development and platelet production
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-975110: TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
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

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IRF7 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 IRF7 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23389942	Breast Carcinoma	Promote immunity (T cell function)	We demonstrate that besides IFN-α, the production by Toll-like receptor (TLR)-activated healthy pDC of IFN-β and TNF-α but not IP-10/CXCL10 nor MIP1-α/CCL3 is impaired by the breast tumor environment. Indeed, recombinant TGF-β1 and TNF-α synergistically blocked IFN-α production of TLR-activated pDC, and neutralization of TGF-β and TNF-α in tumor-derived supernatants restored pDCs' IFN-α production.Importantly, we identified TGF-β and TNF-α as major soluble factors involved in TApDC functional alteration. Mechanisms of type I IFN inhibition did not involve TLR downregulation but the inhibition of IRF-7 expression and nuclear translocation in pDC after their exposure to tumor-derived supernatants or recombinant TGF-β1 and TNF-α.
29422611	Lung Carcinoma	Inhibit immunity	Meanwhile, IRF7 enhanced constitutive PD-L1 expression, which was independent of IFN-γ though directly promote transcription of PD-L1, leading to abrogating cytotoxic T lymphocytes (CTLs) generation which could be restored by anti-PD-L1 antibody, or siRNA-IRF7.
28092673	Melanoma; Lung Carcinoma	Promote immunity	IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice. Importantly, IRF7 expression levels negatively correlated with the G-MDSC frequency and tumor metastasis, as well as S100A9 expression, in cancer patients.
28027521	Breast Carcinoma	Promote immunity	Breast cancer cells which express an innate immune signature regulated by interferon regulatory factor 7 (IRF7) have reduced metastatic potential. Higher levels of the IRF7 signature were significantly associated with a decreased bone metastases risk: (HR = 0.76 for a 50 unit increase, 95% CI, 0.62-0.94, p = 0.012).
22820642	Breast Carcinoma	Promote immunity	Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Restoration of Irf7 in tumor cells or administration of interferon led to reduced bone metastases and prolonged survival time. We confirmed the clinical relevance of these findings in over 800 patients in which high expression of Irf7-regulated genes in primary tumors was associated with prolonged bone metastasis-free survival.

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
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 IRF7 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	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
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 IRF7 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	-0.179	0.684
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.023	0.99
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.294	0.836
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.497	0.134
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.414	0.86
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.603	0.842
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.243	0.603
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.548	0.62
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.164	0.899
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.904	0.59
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	0.421	0.866
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.051	0.718

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IRF7 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	1

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IRF7. 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	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IRF7. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IRF7. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IRF7. 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	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IRF7 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IRF7 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IRF7
Name	interferon regulatory factor 7
Aliases	IMD39; IRF-7HA; IRF7B; IRF7C; IRF7H; IRF-7; interferon regulatory factor-7H
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IRF7 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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