TISIDB

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
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	Cytoplasm. Nucleus. Note=Translocated into the nucleus in response to phosphorylation.
Domain	PF00017 SH2 domain PF01017 STAT protein PF02864 STAT protein PF02865 STAT protein
Function	Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.

> Gene Ontology [ TOP ]
Biological Process	GO:0007259 JAK-STAT cascade GO:0097696 STAT cascade
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04630 Jak-STAT signaling pathway
Reactome	-

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between STAT4 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 STAT4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24958858	Prostate Neoplasm	Promote immunity (T cell function); increase the efficacy of immunotherapy	Interrogation of mechanism showed that testosterone regulates T-helper 1 (Th1) differentiation by inhibiting IL-12-induced Stat4 phosphorylation: in murine models, we determined that androgen receptor binds a conserved region within the phosphatase, Ptpn1, and consequent up-regulation of Ptpn1 then inhibits IL-12 signaling in CD4 T cells.
21998209	lymphoma	Promote immunity	Treatment with the proteasome inhibitor bortezomib reversed chemotherapy-induced STAT4 deficiency and defective IFN-gamma production. We conclude that acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy, results that have important implications for the design of optimal immunotherapy for lymphoma. Furthermore, treatment of control PBMC cultures or a natural killer cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and diminished, IL-12-induced IFN-gamma production.

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
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 STAT4 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	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
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 STAT4 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	-0.124	0.717
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.179	0.777
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.087	0.873
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.554	0.229
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.192	0.416
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.255	0.895
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.604	0.165
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.78	0.364
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.341	0.736
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.067	0.228
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	0.592	0.669
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.294	0.0932

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of STAT4 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	11.1	6.8	4.3	0.443
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	11.1	8.5	2.6	0.702
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
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	23.1	0	23.1	0.223
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	2.6	0	2.6	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	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	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of STAT4. 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	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of STAT4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STAT4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of STAT4. 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	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of STAT4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between STAT4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	STAT4
Name	signal transducer and activator of transcription 4
Aliases	SLEB11
Chromosomal Location	2q32.2-q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting STAT4 collected from DrugBank database.

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

Browse STAT4