TISIDB

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
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	-
Domain	PF03301 Tryptophan 2
Function	Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety.

> Gene Ontology [ TOP ]
Biological Process	GO:0006084 acetyl-CoA metabolic process GO:0006568 tryptophan metabolic process GO:0006569 tryptophan catabolic process GO:0006576 cellular biogenic amine metabolic process GO:0006586 indolalkylamine metabolic process GO:0006637 acyl-CoA metabolic process GO:0006732 coenzyme metabolic process GO:0006790 sulfur compound metabolic process GO:0009072 aromatic amino acid family metabolic process GO:0009074 aromatic amino acid family catabolic process GO:0009308 amine metabolic process GO:0009310 amine catabolic process GO:0016054 organic acid catabolic process GO:0019439 aromatic compound catabolic process GO:0019441 tryptophan catabolic process to kynurenine GO:0019442 tryptophan catabolic process to acetyl-CoA GO:0035383 thioester metabolic process GO:0042180 cellular ketone metabolic process GO:0042402 cellular biogenic amine catabolic process GO:0042430 indole-containing compound metabolic process GO:0042436 indole-containing compound catabolic process GO:0042537 benzene-containing compound metabolic process GO:0044106 cellular amine metabolic process GO:0044270 cellular nitrogen compound catabolic process GO:0044282 small molecule catabolic process GO:0046218 indolalkylamine catabolic process GO:0046700 heterocycle catabolic process GO:0051186 cofactor metabolic process GO:0070189 kynurenine metabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process GO:1901605 alpha-amino acid metabolic process GO:1901606 alpha-amino acid catabolic process
Molecular Function	GO:0004833 tryptophan 2,3-dioxygenase activity GO:0016597 amino acid binding GO:0016701 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen GO:0019825 oxygen binding GO:0020037 heme binding GO:0031406 carboxylic acid binding GO:0043168 anion binding GO:0046906 tetrapyrrole binding GO:0051213 dioxygenase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00380 Tryptophan metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-6788656: Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-71240: Tryptophan catabolism

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TDO2 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 TDO2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23144293	Brain neoplasm	Inhibit immunity	Further, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR).
25132599	glioblastoma	Inhibit immunity	Accordingly, gene expression profile analyses revealed negative correlation of FKBP52 and TDO in glial and neural tumors and in normal brain. Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506 enhanced TDO expression and activity in glioblastoma cells.

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
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 TDO2 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	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
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 TDO2 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	-0.041	0.947
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.892	0.529
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.596	0.534
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.134	0.0667
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.537	0.629
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.883	0.165
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.103	0.143
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.007	0.379
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.118	0.383
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.019	0.989
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	1.19	0.5
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.051	0.793

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TDO2 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	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	0	5.9	-5.9	0.447
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	0	9.1	-9.1	0.458
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	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	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TDO2. 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	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TDO2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TDO2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TDO2. 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	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TDO2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TDO2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TDO2
Name	tryptophan 2,3-dioxygenase
Aliases	TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location	4q31-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TDO2 collected from DrugBank database.

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

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