Browse IDO1

Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
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
 
Subcellular Location Cytoplasm, cytosol
Domain PF01231 Indoleamine 2
Function

Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885).

> Gene Ontology
 
Biological Process GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0002237 response to molecule of bacterial origin
GO:0002507 tolerance induction
GO:0002517 T cell tolerance induction
GO:0002532 production of molecular mediator involved in inflammatory response
GO:0002534 cytokine production involved in inflammatory response
GO:0002544 chronic inflammatory response
GO:0002643 regulation of tolerance induction
GO:0002645 positive regulation of tolerance induction
GO:0002664 regulation of T cell tolerance induction
GO:0002666 positive regulation of T cell tolerance induction
GO:0002676 regulation of chronic inflammatory response
GO:0002678 positive regulation of chronic inflammatory response
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002695 negative regulation of leukocyte activation
GO:0002828 regulation of type 2 immune response
GO:0002830 positive regulation of type 2 immune response
GO:0006568 tryptophan metabolic process
GO:0006569 tryptophan catabolic process
GO:0006576 cellular biogenic amine metabolic process
GO:0006586 indolalkylamine metabolic process
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007565 female pregnancy
GO:0007626 locomotory behavior
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:0016053 organic acid biosynthetic process
GO:0016054 organic acid catabolic process
GO:0019439 aromatic compound catabolic process
GO:0019441 tryptophan catabolic process to kynurenine
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032496 response to lipopolysaccharide
GO:0032613 interleukin-10 production
GO:0032615 interleukin-12 production
GO:0032653 regulation of interleukin-10 production
GO:0032655 regulation of interleukin-12 production
GO:0032693 negative regulation of interleukin-10 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032945 negative regulation of mononuclear cell proliferation
GO:0033555 multicellular organismal response to stress
GO:0034275 kynurenic acid metabolic process
GO:0034276 kynurenic acid biosynthetic process
GO:0036269 swimming behavior
GO:0042092 type 2 immune response
GO:0042098 T cell proliferation
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0042130 negative regulation of T cell proliferation
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:0044283 small molecule biosynthetic process
GO:0044706 multi-multicellular organism process
GO:0046218 indolalkylamine catabolic process
GO:0046394 carboxylic acid biosynthetic process
GO:0046651 lymphocyte proliferation
GO:0046700 heterocycle catabolic process
GO:0050670 regulation of lymphocyte proliferation
GO:0050672 negative regulation of lymphocyte proliferation
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050868 negative regulation of T cell activation
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0070189 kynurenine metabolic process
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070229 negative regulation of lymphocyte apoptotic process
GO:0070230 positive regulation of lymphocyte apoptotic process
GO:0070231 T cell apoptotic process
GO:0070232 regulation of T cell apoptotic process
GO:0070233 negative regulation of T cell apoptotic process
GO:0070234 positive regulation of T cell apoptotic process
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070664 negative regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0071887 leukocyte apoptotic process
GO:0072330 monocarboxylic acid biosynthetic 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
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:2000106 regulation of leukocyte apoptotic process
GO:2000107 negative regulation of leukocyte apoptotic process
GO:2000108 positive regulation of leukocyte apoptotic process
Molecular Function GO:0004833 tryptophan 2,3-dioxygenase activity
GO:0009055 electron carrier activity
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:0020037 heme binding
GO:0033754 indoleamine 2,3-dioxygenase activity
GO:0046906 tetrapyrrole binding
GO:0051213 dioxygenase activity
Cellular Component GO:0030485 smooth muscle contractile fiber
GO:0032421 stereocilium bundle
GO:0043292 contractile fiber
GO:0044449 contractile fiber part
GO:0098862 cluster of actin-based cell projections
> KEGG and Reactome Pathway
 
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
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IDO1 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
 
  Literatures describing the relation between IDO1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28212885Myeloid NeoplasmInhibit immunity (T cell function)Human macrophages exposed to epinephrine and TNFα, or macrophages generated in 6day cultures in the presence of epinephrine, expressed high levels of COX-2, IDO and IL-10, and strongly suppressed both the proliferation and IFNγ production of CD8+T cells.
28179106GlioblastomaInhibit immunityThe enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity.
26979392Melanoma; Breast CarcinomaInhibit immunityThe addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment.
26964621Lung CarcinomaInhibit immunity (T cell function)Here, we show that IDO activity induced by STING activity in the tumor microenvironment (TME) promoted the growth of Lewis lung carcinoma (LLC).
26837767Hepatocellular CarcinomaInhibit immunity (T cell function)Collectively, our findings suggest that the HIF-1α/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network.
26041736MelanomaInhibit immunity (T cell function)This work demonstrates that melanoma-derived Wnt5a ligand upregulates the durable expression and activity of the indoleamine 2,3-dioxygenase-1 (IDO) enzyme by local DCs in a manner that depends upon the β-catenin signaling pathway.
25984582Colon CarcinomaInhibit immunity (T cell function)We found that DCs exposed to butyrate express the immunosuppressive enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and aldehyde dehydrogenase 1A2 (Aldh1A2), promote conversion of naive T-cells into immunosuppressive forkhead box P3(+) (FoxP3(+)) Tregs (regulatory T-cells) and suppress conversion of naive T-cells into pro-inflammatory interferon (IFN)-γ-producing cells.
25814664ThymomaInhibit immunity (T cell function)Taken together, DC-based immune response mediated by interferon-γ-induced IDO expression via GSK-3β activity not only regulates CD8(+) T-cell proliferation and cytotoxic T lymphocyte activity but also modulates OVA-pulsed DC vaccination against EG7 thymoma.
22569001Gastric CarcinomaInhibit immunity (T cell function)Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown.
29355622MelanomaInhibit immunity; immunotherapy targetWe here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP).
24561793Chronic Lymphocytic LeukemiaInhibit immunityChronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of immunosuppressive type 2 skewed macrophages.
24517146Thyroid Gland CarcinomaInhibit immunity (T/NK cell function)Indoleamine 2,3-dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment.
18471709Pancreatic Ductal AdenocarcinomaInhibit immunity (recruit Treg infiltration); immunotherapy targetExpression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. In addition, inhibition of IDO in PDA patients can be useful to enhance immunotherapeutic strategies.
18318466Breast CarcinomaInhibit immunity (T cell function)Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors. Based on available information in the NCI database about menadione in different mouse models of cancer, we evaluated whether menadione, administered at levels near the maximum tolerated dose (MTD), would cooperate with paclitaxel in the MMTV-Neu transgenic mouse model of breast cancer, an assay where the antitumor efficacy of various IDO inhibitors has previously been demonstrated.
28365507Prostate carcinoma; colorectal carcinoma; pancreatic carcinoma; cervical carcinoma; gastric carcinoma; ovarian carcinoma; head and neck neoplasm; lung carcinomaInhibit immunity (T cell function); resistant to immunotherapyIn clinicopathologic study, a series ofhuman tumors including prostatic, colorectal, pancreatic, cervical, gastric, ovarian, head, lung, etc. over-express human IDO1 in a constitutive way. Overexpression of IDO1 leads to three downstream alterations that reduces sensitivity to immunotherapy. Firstly, overexpresson of IDO1 accelerated Tryptophan metabolism, leading to activation of GCN2 stress kinase pathway, increasing IL-6 and CCL2, as well as activation of mTOR pathway. These cause cell cycle arrest and autophagy of cytotoxic T cells, also downregulate TCR ζ chain of T cell to indirectly cause T cell anergy and thus affect immune cells, such as CD8+ T cells, NK cells and NK-T cells, through cytotoxic and cytostatic effects. Secondly, overexpression of IDO1 increases Kynurenine metabolite production, first leading to activation of AhR endogenous ligands to inhibit TH17 cell differentiation, then also inhibit effector T cell survival. Elevated toxic Kynurenine also selectively induces TH1 and thymocyte apoptosis as well as favouring T reg cell differentiation. Through CTLA-4 interaction of T reg cell with DCs, it helps suppression of effector T responses. Furthermore, IDO-expressing DCs also inhibit T cell activation via bystander suppression. On the other hand, increased Kynurenine production regulate NK cell function by two independent ways. Firstly, altering the expression and function of NKp46 triggering recptor and NKG2D triggering recptor. Secondly, reducing NK cytokine production, such as IFN-γ and TNF-α. Lastly, overexpression of IDO1 with the presence of high expression level of HLA-E could lead to downregulation of NKG2C activating recptor, thus enhance the binding to NKG2C inhibitory receptor. Thus, overexpression of IDO1 in tumors reduces the sensitivity and effectiveness of T cell, correlating to por prognosis and reduced survival of patients.
27418644Plasma cell myelomaInhibit immunityWhen targeted by an anti-CD38 mAb, suppressive T-cell function by OCs is alleviated, associated with downregulation of HVEM and IDO.
19366986MelanomaInhibit immunityThe immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining lymph nodes (TDLNs), where it can potently activate Foxp3+ regulatory T cells (Tregs). IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion. In vivo, using a model of established B16 melanoma, the combination of an IDO-inhibitor drug plus antitumor vaccine caused up-regulation of IL-6 in pDCs and in situ conversion of a majority of Tregs to the TH17 phenotype, with marked enhancement of CD8+ T-cell activation and antitumor efficacy.
28470686Pancreatic Carcinoma; Ampulla of Vater CarcinomaInhibit immunity (T cell function)Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p?=?0.002), Gal-9 (p?=?0.003), HVEM (p?=?0.001), IDO (p?=?0.049), HLA-G (p?=?0.004) and high CD8/FoxP3 TIL ratio (p?=?0.006) were associated with improved cancer-specific survival.
23440412Breast CarcinomaInhibit immunity (T cell function)The proportion of MDSCs with the phenotype of CD45(+)CD13(+)CD33(+)CD14(-)CD15(-) significantly increased in primary cancer tissues and patients' peripheral blood. IDO expression was significantly upregulated in MDSCs isolated from fresh breast cancer tissues (fresh MDSCs [fMDSCs]), which correlated with increased infiltration of Foxp3(+) regulatory T cells in tumors and lymph node metastasis in patients.
19665763Ovarian CarcinomaInhibit immunity (infiltration)IDO expression was immunohistochemically scored in surgically-resected ovarian cancer tissues (n=60), and its association with tumor-infiltrating lymphocyte (TIL) count or patient survival was analyzed. Next, IDO cDNA was transfected into the human ovarian carcinoma cell line SKOV3, establishing stable clones of IDO-overexpressing cells (SK-IDO). High IDO expression in tumor cells was found in 34 (56.7%) cases and was correlated with a reduced number of CD8+ TIL.
27575718Colorectal CarcinomaInhibit immunity (infiltration)We detected increased T cell infiltration in the tumor microenvironment after activation of the immune system with the combination of IDO inhibition by the small-molecule immunotherapy agent and immunogenic cell death induced by PDT.
23752227B16 Malignant MelanomaInhibit immunity (infiltration); Inhibit immunity (T cell function); resistant to immunotherapyHere, we examine the inhibitory role of indoleamine 2,3-dioxygenase (IDO) on the antitumor efficacy of CTLA-4 blockade. To highlight the therapeutic relevance of these findings, we show that CTLA-4 blockade strongly synergizes with IDO inhibitors to mediate rejection of both IDO-expressing and nonexpressing poorly immunogenic tumors, emphasizing the importance of the inhibitory role of both tumor- and host-derived IDO. This effect was T cell dependent, leading to enhanced infiltration of tumor-specific effector T cells and a marked increase in the effector-to-regulatory T cell ratios in the tumors. Overall, these data demonstrate the immunosuppressive role of IDO in the context of immunotherapies targeting immune checkpoints and provide a strong incentive to clinically explore combination therapies using IDO inhibitors irrespective of IDO expression by the tumor cells.
22258454MelanomaInhibit immunity (NK cell function)We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2).
27470968Gastrointestinal Stromal TumorInhibit immunity (T cell function); immunotherapy targetPD-1 and PD-L1 blockade in vivo each had no efficacy alone but enhanced the antitumor effects of imatinib by increasing T-cell effector function in the presence of KIT and IDO inhibition.
24696473Nasopharyngeal CarcinomaInhibit immunity (T cell function)Here, we showed that some macrophages in the tumor stroma of nasopharyngeal carcinoma (NPC) tissue expressed the immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) more strongly than did tumor cells. Moreover, the activation of IDO in response to EBV infection of MDMs suppressed the proliferation of T cells and impaired the cytotoxic activity of CD8(+) T cells, whereas the inhibition of IDO activity with 1-methyl-l-tryptophan (1-MT) did not affect T cell proliferation and function.
20801903Acute Myeloid LeukemiaInhibit immunity (T cell function)Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan
19739080Ovarian CarcinomaInhibit immunity (T cell function)The immunosuppression of CD4(+) T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase.
19050070Acute Myeloid LeukemiaInhibit immunityHigh INDO expression was correlated to significantly shortened overall and relapse-free survival. Correlation of INDO expression to relevant known prognostic factors and survival identified high INDO expression as a strong negative independent predicting variable for overall and relapse-free survival.
19010841Endometrial CarcinomaInhibit immunityHowever, in vivo tumor growth was markedly enhanced in AMEC-IDO-xenografted nude mice when compared with AMEC-pcDNA-xenografted mice. Finally, oral administration of the IDO inhibitor 1-methyl-D-tryptophan in combination with paclitaxel in AMEC-IDO-xenografted mice strongly potentiated the antitumor effect of paclitaxel, resulting in significantly prolonged survival.
17234791Breast Carcinoma; MelanomaInhibit immunity (T cell function)However, the D isomer was significantly more effective in reversing the suppression of T cells created by IDO-expressing dendritic cells, using both human monocyte-derived dendritic cells and murine dendritic cells isolated directly from tumor-draining lymph nodes. In vivo, the d isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamide, paclitaxel, or gemcitabine, when tested in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer.
29685162Colon CarcinomaInhibit immunity (T cell function); decrease the efficacy of immunotherapyThese findings indicate that miR-153 inhibits IDO1 expression in colon cancer cells and is a tumor-suppressive miRNA that enhances CAR T cell immunotherapy.
29595533Esophageal CarcinomaInhibit immunity immunotherapy targetIDO1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker.
27923823Nasopharyngeal CarcinomaInhibit immunity; immunotherapy targetIndoleamine 2,3-dioxygenase (IDO), an IFNγ-inducible enzyme, is a major inducer of immune tolerance during tumor development; therefore, inhibition of the IDO pathway is an important modality for cancer treatment.
23986400MelanomaInhibit immunity (infiltration)In the current report, we show that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3(+) regulatory T cells (T(regs)), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8(+) T cell infiltration.
23960017Hepatocellular CarcinomaInhibit immunity (T cell function)Human CD14+ CTLA-4+ regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma. CD14(+) DCs significantly suppress T-cell response in vitro through interleukin (IL)-10 and indoleamine-2,3-dioxygenase (IDO). Unexpectedly, CD14(+) DCs expressed high levels of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1, and CTLA-4 was found to be essential to IL-10 and IDO production. So, we identified a novel human tumor-induced regulatory DC subset, which suppresses antitumor immune response through CTLA-4-dependent IL-10 and IDO production, thus indicating the important role of nonregulatory T-cell-derived CTLA-4 in tumor-immune escape or immunosuppression.
23925295Breast Carcinoma; MelanomaInhibit immunityUsing murine models of breast cancer and melanoma, we elucidated a tumor immunoevasion mechanism whereby loss of tumor-expressed TGFBR3/sTGFBR3 enhanced TGF-β signaling within locoregional DC populations and upregulated both the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in plasmacytoid DCs and the CCL22 chemokine in myeloid DCs. Alterations in these DC populations mediated Treg infiltration and the suppression of antitumor immunity.
23871358Acute Myeloid LeukemiaInhibit immunityWe envisage future treatment protocols, in which systemic immune activators, such as vaccines, dendritic cell-based therapies, engineered variants of IL-2, or IL-15, are combined with agents that counter immunosuppression mediated by, e.g., the PD/PDL interaction, CTLA-4, CD200, reactive oxygen species, IDO expression, CXCR4, or the KIR/class I interaction, based on characteristics of the prevailing malignant clone.
20124451Colon Carcinoma; Pancreatic CarcinomaInhibit immunityExpression of indoleamine-2,3-dioxygenase (IDO; IDO1), a rate-limiting enzyme in the catabolism of tryptophan into kynurenine, contributes to this immune evasion. Substantiating the fundamental role of tumor cell-derived IDO expression, hydroxyamidines control the growth of IDO-expressing tumors in Ido1-deficient mice. These activities can be attributed, at least partially, to the increased immunoreactivity of lymphocytes found in tumors and their draining lymph nodes and to the reduction in tumor-associated regulatory T cells.
28765120Ovarian CarcinomaInhibit immunity (infiltration); Resistant to immunotherapyCelecoxib treatment promoted immune rejection of IDO1-expressing human tumor xenografts in immunodeficient mice reconstituted with human allogeneic lymphocytes. This effect was associated with a reduced expression of IDO1 in those ovarian SKOV3 tumors and an increased infiltration of CD3+and CD8+cells. Our results highlight the role of COX-2 in constitutive IDO1 expression by human tumors and substantiate the use of COX-2 inhibitors to improve the efficacy of cancer immunotherapy, by reducing constitutive IDO1 expression, which contributes to the lack of T-cell infiltration in "cold" tumors, which fail to respond to immunotherapy.
28751450GlioblastomaInhibit immunityGBM IDO1 mRNA levels positively correlated with increased gene expression for markers of cytolytic and regulatory T cells, in addition to decreased patient survival.
27994058Thyroid Gland CarcinomaInhibit immunityRecently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared with normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune escape.
24452999Melanoma; LymphomaInhibit immunity (infiltration)Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment. These IDO-expressing humanized MSCs (MSC-IDO) were capable of suppressing T-lymphocyte proliferation in vitro. In melanoma and lymphoma tumor models, MSC-IDO promoted tumor growth in vivo, an effect that was reversed by the IDO inhibitor 1-methyl-tryptophan. We found that MSC-IDO dramatically reduced both tumor-infiltrating CD8(+) T cells and B cells.
22932670GliomaInhibit immunityIDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Coincidently, both IDO-competent and deficient mice showed a survival advantage bearing IDO-deficient brain tumors, when compared with IDO-competent brain tumors. IDO deficiency was also associated with lower GITR expression levels on Tregs.
22822050Lung CarcinomaInhibit immunityInvestigating the impact of Ido1 gene disruption in mouse models of oncogenic KRAS-induced lung carcinoma and breast carcinoma-derived pulmonary metastasis, we have found that IDO deficiency resulted in reduced lung tumor burden and improved survival in both models. Micro-computed tomographic (CT) imaging further revealed that the density of the underlying pulmonary blood vessels was significantly reduced in Ido1-nullizygous mice. IDO deficiency in vivo negatively impacted both vascularization and IL-6–dependent, MDSC-driven immune escape, establishing IDO as an overarching factor directing the establishment of a protumorigenic environment.
22108515Colorectal CarcinomaInhibit immunityCarcinomas may create an immunosuppressive state via IDO1 expression. Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC.
22033321MelanomaInhibit immunityThe expression of IDO and forkhead box P3 (Foxp3) in the sentinel lymph nodes was determined by immunohistochemistry and correlated with progression-free survival and overall survival. High IDO expression was correlated with a significant higher frequency of Foxp3-positive cells in uninvaded lymph nodes (p = 0.016). The presence of IDO expression in the sentinel nodes was not associated with an increased frequency of circulating regulatory T cells (Tregs) but was significantly correlated with an increased mean fluorescence intensity of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) in Tregs (p = 0.019).
21742973T Lymphoblastic LymphomaInhibit immunityTryptophan depletion by IDO-expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. These findings highlight the ability of IDO-expressing tumor cells to thrive in a tryptophan-depleted microenvironment by expressing a novel, highly tryptophan-specific transporter, which is resistant to inhibition by most other amino acids.
21616522Vulvar Squamous Cell CarcinomaInhibit immunityExpression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitment of FOXP3-expressing regulatory T cells in cancer nests. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age.
20350764Infiltrating Cervical CarcinomaInhibit immunityIDO expression was positively correlated with clinical stage, lymph node metastasis, and lymph-vascular space invasion, but not with histological type. Patients with diffuse IDO expression had significantly reduced overall survival (OS) and disease-free survival (DFS) compared to patients with no IDO expression.
29805749Esophageal CarcinomaInhibit immunityHigh IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells.
29746927Lung CarcinomaInhibit immunityIndoleamine 2,3-dioxygenase 1 inhibition targets anti-PD1-resistant lung tumors by blocking myeloid-derived suppressor cells. IDO1 was overexpressed in tumor-infiltrating leukocytes, and plasma Kyn levels were increased, in 344SQ_R vs. 344SQ_P. The IDO1 inhibitor INCB023843 retarded tumor growth and reduced lung metastases in 344SQ_R. IDO1 was expressed at higher levels in F4/80+Gr1intCD11b+ myeloid-derived suppressor cells (MDSCs) that were prominent in 344SQ_R. The INCB023843 reduced IDO1 expression and percentages of these MDSCs while increasing CD8+ T cells infiltration, hence reactivating antitumor T-cell responses in 344SQ_R.
29719533Breast CarcinomaInhibit immunityConcentrating on IDO and MVD, the patients with IDO expression or high MVD level had poorer prognosis compared with no IDO expression [P = 0.047 for progress-free survival (PFS)] and low MVD level (P = 0.019 for OS); the patients with IDO expression and high MVD level had a tendency with shorter overall survival when compared with non IDO expression, low MVD level, or both (P = 0.062 for OS). MCF-7 cells, which produce high level of IDO and metabolize tryptophan, promoted human umbilical vein endothelial cells (HUVEC) proliferation significantly in co-culture system. These results suggest that IDO could promote angiogenesis in breast cancer, providing a novel, potentially effective molecular or gene therapy target for angiogenesis inhibition in the future.
18952840Skin PapillomaInhibit immunityThe induced IDO-mediated inhibitory activity in this subset of pDCs was potent, dominantly suppressing the T cell stimulatory activity of other DCs that comprise the major fraction of dLN DCs. Consistent with the hypothesis that T cell suppressive, IDO(+) pDCs elicited by PMA exposure create local immune privilege that favors tumor development, IDO-deficient mice exhibited a robust tumor-resistant phenotype in the standard DMBA/PMA 2-stage carcinogenesis model of skin papilloma formation.
17565341Cutaneous MelanomaInhibit immunityOur results indicate that tolerogenic DCs and suppressor T lymphocytes are present in melanoma at all stages of disease progression. In primary melanoma, TGFbeta2 is likely to render peripheral DCs tolerogenic, while in lymph nodes IDO and TGFbeta1 may have a major effect.
23384943Pan-CancerInhibit immunityMechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19?CD38?CD1d?IgM?CD147? expression signature, along with expression of additional key regulatory molecules including IL-10, CD25, and indoleamine-2,3-dioxygenase
21873989gastrointestinal stromal tumorInhibit immunityImatinib therapy activated CD8(+) T cells and induced regulatory T cell (T(reg) cell) apoptosis within the tumor by reducing tumor-cell expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido).
16888001Breast CarcinomaInhibit immunityEnhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line.
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
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
  Statistical results of IDO1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
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
 
Points in the above scatter plot represent the expression difference of IDO1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1750.777
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1310.923
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.220.858
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3050.617
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1580.886
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.4830.737
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.2650.0577
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.4970.212
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.9990.452
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.670.228
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1670.585
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.4090.2
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IDO1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.44.13.30.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.45.12.30.647
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.3014.30.238
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IDO1. 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
 
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IDO1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IDO1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IDO1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IDO1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IDO1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIDO1
Nameindoleamine 2,3-dioxygenase 1
Aliases IDO; INDO; indoleamine-pyrrole 2,3 dioxygenase; IDO-1; indolamine 2,3 dioxygenase; indole 2,3-dioxygenase; i ......
Chromosomal Location8p12-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IDO1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting IDO1.
ID Name Drug Type Targets #Targets
DB00435Nitric OxideSmall MoleculeGUCY1A2, IDO1, MT1A3