Ask about this productRelated genes to: TDO2 Blocking Peptide
- Gene:
- TDO2 NIH gene
- Name:
- tryptophan 2,3-dioxygenase
- Previous symbol:
- -
- Synonyms:
- TDO, TPH2
- Chromosome:
- 4q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 1989-05-29
- Date modifiied:
- 2016-10-25
Related products to: TDO2 Blocking Peptide
Related articles to: TDO2 Blocking Peptide
- Acute myeloid leukemia (AML) involves immune dysregulation and evasion, in which tryptophan catabolism via the kynurenine pathway (KP) is central. Leukemic blasts often overexpress indoleamine 2,3-dioxygenase-1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2), driving excess L-kynurenine (Kyn) production. Kyn activates the aryl hydrocarbon receptor (AhR), inducing interleukin-6 (IL-6) secretion and STAT3 phosphorylation with NF-κB co-activation, sustaining chronic inflammation. Concomitantly, KP activation is immunosuppressive: Kyn biases T cells toward FoxP3+ regulatory phenotypes, drives exhaustion of T and NK cells, and impairs dendritic and B-cell function, yielding an immunosuppressive milieu rich in IL-10 and IL-35. Together, these actions link chronic inflammation to immune tolerance in AML. By contrast, while upstream enzymes (IDO1/TDO2) are well studied, downstream KP metabolites remain poorly characterized in AML. In other systems, kynurenic acid (KYNA) mediates anti-inflammatory GPR35/AhR signaling, whereas 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) generate reactive oxygen species, activate NF-κB-dependent cytokine cascades, and induce T-cell apoptosis. Collectively, the extended KP emerges as a nexus linking inflammatory signaling and immunosuppression in AML, with implications for disease progression, immune escape, and resistance, warranting further investigation. - Source: PubMed
Publication date: 2026/05/22
Wawrzak-Pienkowska KatarzynaGolonko AleksandraIgnatiuk DianaSwidnicka-Siergiejko AgnieszkaPienkowski TomaszKurek Krzysztof - Hepatocellular carcinoma (HCC) develops within a complex microenvironment in which cancer-associated fibroblasts (CAFs) are abundant, yet their heterogeneity and functional roles remain incompletely understood. Here, we integrated multi-site single-cell RNA sequencing of Normal liver, primary Tumor, portal vein tumor thrombus (PVTT), and metastatic Lymph node samples with bulk transcriptomic analysis, cell-cell communication inference, and functional assays to define stromal programs associated with HCC progression. We identified four transcriptionally distinct CAF subsets: SGCA mCAFs, POSTN mCAFs, TDO2 CAFs, and CXCL14 iCAFs, each showing site-specific distribution and distinct prognostic relevance. Among them, POSTN mCAFs were enriched for extracellular matrix organization and integrin signaling, and their signatures were consistently associated with poor overall survival across independent cohorts. Ligand-receptor analysis identified POSTN mCAFs as highly connected stromal hubs communicating with malignant and myeloid cells through ECM-integrin, collagen-SDC4, and chemokine pathways. Consistently, tumor-derived POSTN-high fibroblasts promoted hepatoma cell proliferation, migration, and invasion in vitro. Together, these findings identify POSTN mCAFs as a transcriptionally distinct and functionally pro-tumorigenic stromal subset in HCC, supporting POSTN-centered stromal programs as candidate markers of aggressive tumor microenvironments and a basis for future mechanistic investigation. - Source: PubMed
Publication date: 2026/05/22
Chen YalinLiu TingtingZhang ShichaoWu Dong - Emphysema is a well-recognized risk factor for lung cancer; however, its influence on the immunologic tumor microenvironment in lung adenocarcinoma remains poorly defined. In this pilot, hypothesis-generating study, immune-related gene expression profiling was performed using archival formalin-fixed paraffin-embedded tumor specimens from 12 patients with lung adenocarcinoma, including the Never-smoker group (never-smokers without emphysema; = 4), the Smoker 1 group (smokers without emphysema; = 3), and the Smoker 2 group (smokers with CT-defined emphysema; = 5). Expression of 770 immune-related genes was analyzed using the nCounter PanCancer IO 360 Panel (NanoString Technologies, Seattle, WA, USA). Compared with the Never-smoker group, tumors from the Smoker 1 group showed marked upregulation of SFRP1, SERPINB5, and IL6, whereas tumors from the Smoker 2 group exhibited increased expression of KIR2DL3, BLK, and WNT2B. Relative to the Smoker 1 group, the Smoker 2 group demonstrated significant upregulation of MMP7, TDO2, and CCL18. Pathway enrichment analysis revealed cytokine-cytokine receptor interaction as the most prominently enriched pathway in both smoker groups, while the IL-17 signaling pathway was preferentially enriched in the Smoker 2 group. In addition, diffusing capacity for carbon monoxide showed significant correlations with immune-related genes including IL-6 and IL-6R. Collectively, these preliminary findings suggest that lung adenocarcinoma arising in emphysematous lungs may be characterized by a distinct pro-inflammatory immune microenvironment. Given the small sample size and potential confounders, these results should be regarded as hypothesis-generating. Emphysema-associated immune remodeling may nevertheless represent an important biological factor worthy of validation in larger, independent cohorts. - Source: PubMed
Publication date: 2026/04/29
Lim Jeong UkKim SeohyeonAn Tai JoonSa Young JoKim Hyo RimPark Chan KwonYoon Hyoung KyuKim Tae-Jung - This study aimed to characterize large and small RNA transcriptomic changes in fibroid xenografts from mice treated with the TDO2 inhibitor 680C91 for two months and to validate selected findings using qRT-PCR, protein analyses, and in vitro fibroid explant models. Large RNA next-generation sequencing revealed that 680C91 induced broad transcriptomic alterations, with enrichment of pathways related to the extracellular space, RNA processing, PI3K/AKT signaling, and calcium signaling. Small RNA sequencing identified enrichment of pathways associated with PI3K/AKT signaling, proteoglycans in cancer, and interleukin signaling. Key differentially expressed genes were validated in xenografts and fibroid explants. Treatment with 680C91 significantly reduced the mRNA expression of VDR, MMP11, MMP14, COL11A1, CBX4, LINC02568, LINC01310, LINC02544, and LINC02182, while increasing miR-584-5p expression. These changes were consistently observed in fibroid explants treated with 680C91 for 48 hours. Corresponding decreases in protein levels of COL11A1, VDR, CBX4, MMP11, and MMP14 were also detected. Additionally, 680C91 inhibited AKT phosphorylation and reduced α-smooth muscle actin and vimentin expression. Importantly, all validated transcripts displayed expression patterns opposite to those observed in fibroid tissues compared with matched myometrium, with more pronounced effects in MED12-mutated tumors. These preclinical findings support TDO2 inhibition as a potential therapeutic strategy for uterine fibroids. - Source: PubMed
Publication date: 2026/05/11
Chuang Tsai-DerWiseman AbigailAlfaro GabrielaPejouhesh Jahromi SaynaPejouhesh Jahromi SepidehBaghdasarian DanielKhorram Omid - Inflammation is a central mediator linking metabolic dysfunction to severe human disease. Imbalance or loss of ovarian hormone (such as in post-menopausal women) contributes to increased risk of cardiovascular diseases, obesity and others. Here, using ovariectomized (OVX) Long-Evans rats as model for estrogen deprivation, we demonstrate that estrogen deprivation induces hepatic inflammation, activates tryptophan catabolism, systemic inflammation and disrupted cholesterol homeostasis. OVX animals gained more weight and developed an atherogenic plasma profile with increased LDL and total cholesterol and reduced HDL levels compared to intact female animals, which was reversed by estradiol (E2) administration. Ovariectomy results in elevation of hepatic pro-inflammation cytokine (e.g. TNFα, IL6), tryptophan catabolic enzymes (e.g. IDO1, and TDO2) and reduced reverse cholesterol associated gene SR-BI expression and E2- administration also suppressed the ovariectomy-induced hepatic inflammation resulting in reduction of TNFα, IL6, IDO1 and TDO2 while elevation of SR-BI expression. Plasma kynurenine, nitric oxide and lactate were elevated upon ovariectomy suggesting increased system Trp-catabolism, inflammation, each was reversed by estrogen. Targeted LC-MS metabolomics analysis revealed enhanced Trp-to-kynurenine flux, elevated lactate, accumulation of citrate/isocitrate/aconitate, and a reduced α-ketoglutarate/aconitate ratio (~ 0.6) restored by estradiol (~ 3.6). Together, our studies suggest a a link between estrogen signaling and hepatic immune-metabolism via regulation of Trp-catabolism, this open up potential novel signaling pathways for treating cardiometabolic disease and hormonal disorders. - Source: PubMed
Publication date: 2026/04/24
Guha PrarthanaRishi AshcharyaChini AvisankarBhat NagashreeGondrala Pavan KBrady BlakeBaniasadi Hamid RPerrotti Linda IMandal Subhrangsu S