TDO2 overexpression

This study highlights the key mechanisms behind BaP-induced immune evasion in LUAD, particularly through the TDO2/AhR axis. It reveals how TDO2 inhibitors can counteract immune checkpoint activation and boost anti-tumor immunity, suggesting new paths for targeted lung cancer immunotherapy. The findings significantly improve our understanding of immune evasion in LUAD and underscore the therapeutic promise of TDO2 inhibition.

The results indicate that correction of aberrant tryptophan catabolism in fibroids could be an effective treatment through its effect to reduce cell proliferation and ECM accumulation.

Selective and potent inhibition of TDO2 does effectively block L-Kynurenine synthesis in the uterus but does not improve the menstrual bleeding pattern in a murine HMB disease model. As the transgenic TDO2 model does not completely mimic L-Kynurenine levels released by uterine fibroids, the predictive validity of this model might be limited. Further models are needed to understand the functional role of TDO2 in uterine fibroids and the pathophysiology of heavy menstrual bleeding.

Overall, TDO2 may be a biomarker for the survival and prognosis of patients with malignant tumors and a potential therapeutic target in the future. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260442, identifier (CRD42021260442).

Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.

In conclusion, we show that Ido1 deficiency aggravates atherosclerosis, but not liver disease, in a newly established NASH and atherosclerosis comorbidity model. Our data indicate that the overexpression of TDO2 is an important mechanism that helps in balancing the kynurenine pathway and inflammation in the liver, but not in the artery wall, which likely determined disease outcome in these two target tissues.

Furthermore, azelnidipine treatment to downregulate TDO2 also decreased liver cancer development in this mouse cancer model. TDO2 is thus not only a useful liver cancer biomarker but a potential drug target for management of liver cancer.

Gene enrichment analysis showed that TDO2 was closely related to immune response. Conclusion :Overall, TDO2 may be a biomarker for survival and prognosis of patients with malignant tumours and a potential therapeutic target in the future.

Our results pointed out that IDO1 and TDO2 could play an essential role in regulating the tumor microenvironment as well as immune tolerance in bladder cancer. Suggesting that IDO1, TDO2 might be a promising novel immunotherapy target for bladder cancer patients.

Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

Together, our study showed that the TDO2/Kyn/AhR/IL-6 signaling pathway was a novel mechanism underlying the malignancy of liver cancer, and suggested that AhR signals might be a valuable therapeutic target for tumor therapy.

Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3β, and polarization of M2 macrophages by upregulating interleukin-8 (IL-8) to accelerate tumor progression in the tumor microenvironment (TME). Collectively, our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC, and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.