TISIDB

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
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=In resting macrophages, localizes in the cytoplasm. Translocated in the nucleus upon IFN-gamma induction.
Domain	PF00605 Interferon regulatory factor transcription factor PF10401 Interferon-regulatory factor 3
Function	Plays a role as a transcriptional activator or repressor (PubMed:25122610). Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a negative regulatory role in cells of the immune system. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001562 response to protozoan GO:0001819 positive regulation of cytokine production GO:0002237 response to molecule of bacterial origin GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006909 phagocytosis GO:0030099 myeloid cell differentiation GO:0031334 positive regulation of protein complex assembly GO:0032496 response to lipopolysaccharide GO:0032609 interferon-gamma production GO:0032615 interleukin-12 production GO:0032649 regulation of interferon-gamma production GO:0032655 regulation of interleukin-12 production GO:0032729 positive regulation of interferon-gamma production GO:0032735 positive regulation of interleukin-12 production GO:0034340 response to type I interferon GO:0034341 response to interferon-gamma GO:0042742 defense response to bacterium GO:0042832 defense response to protozoan GO:0043254 regulation of protein complex assembly GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044089 positive regulation of cellular component biogenesis GO:0044110 growth involved in symbiotic interaction GO:0044116 growth of symbiont involved in interaction with host GO:0044117 growth of symbiont in host GO:0044126 regulation of growth of symbiont in host GO:0044130 negative regulation of growth of symbiont in host GO:0044144 modulation of growth of symbiont involved in interaction with host GO:0044146 negative regulation of growth of symbiont involved in interaction with host GO:0045926 negative regulation of growth GO:0060260 regulation of transcription initiation from RNA polymerase II promoter GO:0060261 positive regulation of transcription initiation from RNA polymerase II promoter GO:0060333 interferon-gamma-mediated signaling pathway GO:0060337 type I interferon signaling pathway GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071346 cellular response to interferon-gamma GO:0071357 cellular response to type I interferon GO:0071396 cellular response to lipid GO:0098542 defense response to other organism GO:2000142 regulation of DNA-templated transcription, initiation GO:2000144 positive regulation of DNA-templated transcription, initiation
Molecular Function	GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-877300: Interferon gamma signaling

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IRF8 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 IRF8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25446897	Melanoma	Promote immunity	Within these, CD103(+) DCs are extremely sparse and yet remarkably capable CTL stimulators. These are uniquely dependent on IRF8, Zbtb46, and Batf3 transcription factors and are generated by GM-CSF and FLT3L cytokines. Regressing tumors have higher proportions of these cells, T-cell-dependent immune clearance relies on them, and abundance of their transcripts in human tumors correlates with clinical outcome.
29316433	Breast carcinoma	Increase the efficacy of immunotherapy	Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.
21159639	Lymphoma	Promote immunity (T cell function)	CXCL12 mediates immunosuppression in the lymphoma microenvironment after allogeneic transplantation of hematopoietic cells. In vivo blocking identified the CXCR4/CXCL12 axis as being critical for Treg attraction toward BCL. In contrast to Tregs, effector T cells displayed low levels of CXCR4 and were not affected by the pharmacologic blockade. Most important, blocking CXCR4 not only reduced Treg migration toward tumor tissue but also enhanced antitumor responses after alloHCT. CXCL12 production was dependent on antigen-presenting cells (APC) located in the lymphoma microenvironment, and their diphtheria-toxin receptor (DTR)-based depletion in CD11c.DTR-Tg mice significantly reduced Treg accumulation within BCL tissue.
19542426	Breast Carcinoma	Promote immunity (T cell function)	CD11b(+)Gr-1(+)-expressing cells, termed myeloid-derived suppressor cells, can mediate immunosuppression and tumor progression. Despite limited differences in phenotype, tumor-induced CD11b(+)Gr-1(+) cells were found to produce a more immunosuppressive cytokine profile than that observed by Cnt CD11b(+)Gr-1(+) cells. Furthermore, when admixed with tumor cells, CD11b(+)Gr-1(+) cells from tumor-bearing mice significantly enhanced neoplastic growth compared with counterpart cells from Cnt mice. However, the protumorigenic behavior of these tumor-induced CD11b(+)Gr-1(+) cells was significantly diminished when the expression of IFN regulatory factor 8, a key myeloid-associated transcription factor, was enhanced.
28356386	Breast Carcinoma	Promote immunity	We recently showed that IRF8 inversely controls MDSC burden in tumor models, particularly the PMN-MDSC subset. In this study, we showed that: 1) tumor growth was associated with a selective expansion of newly defined IRF8lo granulocyte progenitors (GPs); 2) tumor-derived GPs had an increased ability to form PMN-MDSCs; 3) tumor-derived GPs shared gene expression patterns with IRF8-/- GPs, suggesting that IRF8 loss underlies GP expansion; and 4) enforced IRF8 overexpression in vivo selectively constrained tumor-induced GP expansion. These findings support the hypothesis that PMN-MDSCs result from selective expansion of IRF8lo GPs, and that strategies targeting IRF8 expression may limit their load to improve immunotherapy efficacy.
19171873	Leukemia	Promote immunity	Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL-induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression.
24957708	acute myeloid leukemia	Promote immunity	Constitutive expression of Irf8 or its target gene Ccl9 identified these genes as potent inhibitors of murine and human leukemias in vivo.
29593283	breast carcinoma; Pancreatic ductal adenocarcinoma	Promote immunity	Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance.
29233972	Melanoma	Promote immunity	In vivo, IRF8 is essential for the anti-tumour effects of Th9 cells in mouse melanoma models. Our results show that IRF8 complexes boost the Th9 program and repress Il4 expression to modulate Th9 cell differentiation. IRF8 functions through a transcription factor complex consisting of IRF8, IRF4, PU.1 and BATF, which binds to DNA and boosts Il9 transcription.
22805310	Soft Tissue Sarcoma	Promote immunity	Using a murine model of soft tissue sarcoma (STS), we show that disruption of the IFN effector molecule IRF8 decreases pSTAT1 and increases uSTAT1 in STS cells, thereby increasing their metastatic potential. Mechanistic investigations revealed that IRF8 suppressed STAT1 transcription by binding the STAT1 promoter.
20585039	B Lymphoblastic Leukemia/Lymphoma	Inhibit immunity	Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a very early age a more aggressive chronic myelogenous leukemia-like disease than mice deficient in IRF-8 alone, correlating with a greater expansion of granulocyte-monocyte progenitors.

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
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 IRF8 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	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
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 IRF8 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	0.202	0.73
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.706	0.685
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.169	0.902
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.198	0.728
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.174	0.901
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.68	0.729
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.579	0.274
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.087	0.448
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.026	0.987
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.794	0.56
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	0.942	0.66
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.209	0.3

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IRF8 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	2.7	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	3.4	0.3	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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	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	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IRF8. 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	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IRF8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IRF8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IRF8. 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	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IRF8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IRF8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IRF8
Name	interferon regulatory factor 8
Aliases	IRF-8; ICSBP; ICSBP1; interferon consensus sequence binding protein 1; H-ICSBP; IMD32A; IMD32B; Interferon c ......
Chromosomal Location	16q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IRF8 collected from DrugBank database.

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

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