Breakdown of chemo-immune resistance by a TDO2-targeted Pt(IV) prodrug via attenuating endogenous Kyn-AhR-AQP4 metabolic circuity and TLS-promoted genomic instability

Chen, Feihong; Xu, Gang; Tian, Wenyuan; Gou, Shaohua

doi:10.1016/j.bcp.2021.114785

Cited by 8 publications

(2 citation statements)

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“…Studies have proven that an overexpression of TDO2 could activate AhR of immune cells and achieve immune escape [36]. It has been confirmed that TDO2 is involved in mediating tumoral immune resistance, which raised considerable interest of targeting TDO2 for cancer immunotherapy [37]. The treatment with a TDO2 inhibitor could promote the function of den-dritic cell and improve T cell mediated immune response, thereby diminishing tumor metastasis in mice [27].…”

Section: Discussionmentioning

confidence: 99%

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

et al. 2022

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Background. Tryptophan 2,3-dioxygenase (TDO) encoded by TDO2, a rate-limiting enzyme in the kynurenine pathway, catabolizes tryptophan to kynurenine, evades immune surveillance, and promotes tumor growth. Although accumulating evidence suggests a crucial role of TDO2 during tumor formation and development, systematic evaluation of TDO2 across human cancers has rarely been reported. Methods. To shed more light on the role of TDO2 in human cancer, we explored the expression profiles of TDO2 and identified its prognostic value in pancancer analysis through TCGA, CCLE, and GTEx databases. We further utilized TCGA data to evaluate the association between TDO2 and tumor immunological features, such as mismatch repair (MMR), tumor immune infiltration, immune checkpoint-related genes, tumor mutational burden (TMB), microsatellite instability (MSI), and DNA methyltransferase (DNMT). Results. TDO2 exhibited different expression levels in various cancer cell lines. Frequently, TDO2 was detected to be highly expressed in the majority of cancers. In addition, high TDO2 expression was correlated with an unfavorable prognosis for patients in KIRP, LGG, TGCT, and UVM. Moreover, high TDO2 expression level positively correlated with higher immune infiltration, especially dendritic cells. Additionally, there is a close relationship between TDO2 and immune checkpoint-related gene markers, such as LAIR1, CD276, NRP1, CD80, and CD86. Finally, correlation analysis has demonstrated a high-correlation between TDO2 and TMB, MSI, MMR, and DNMT of multiple cancer types. Conclusion. Therefore, our results suggest that TDO2 can function as a potential prognostic biomarker due to its role in tumor immunity regulation.

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Section: Discussionmentioning

confidence: 99%

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

et al. 2022

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“…As a member of our risk score model, tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the commitment step of the KYN metabolic process, which subsequently activates the AhR and contributes to an immunosuppressive TME, and supports the cancer immune escape [40,41]. FAR2, namely the fatty acyl-CoA reductase 2, has been found to be localized in the peroxisome and participate in the first step of wax biosynthesis [42].…”

Section: Discussionmentioning

confidence: 99%

The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer

et al. 2022

Cancers

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Cervical cancer is the most frequently diagnosed malignancy in the female reproductive system. Conventional stratification of patients based on clinicopathological characters has gradually been outpaced by a molecular profiling strategy. Our study aimed to identify a reliable metabolism-related predictive signature for the prognosis and anti-tumor immunity in cervical cancer. In this study, we extracted five metabolism-related hub genes, including ALOX12B, CA9, FAR2, F5 and TDO2, for the establishment of the risk score model. The Kaplan-Meier curve suggested that patients with a high-risk score apparently had a worse prognosis in the cervical cancer training cohort (TCGA, n = 304, p < 0.0001), validation cohort (GSE44001, n = 300, p = 0.0059) and pan-cancer cohorts (including nine TCGA tumors). Using a gene set enrichment analysis (GSEA), we observed that the model was correlated with various immune-regulation-related pathways. Furthermore, pan-cancer cohorts and immunohistochemical analysis showed that the infiltration of tumor infiltrating lymphocytes (TILs) was lower in the high-score group. Additionally, the model could also predict the prognosis of patients with cervical cancer based on the expression of immune checkpoints (ICPs) in both the discovery and validation cohorts. Our study established and validated a metabolism-related prognostic model, which might improve the accuracy of predicting the clinical outcome of patients with cervical cancer and provide guidance for personalized treatment.

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The role of Platinum(IV)-based antitumor drugs and the anticancer immune response in medicinal inorganic chemistry. A systematic review from 2017 to 2022

Chen

Zhang

et al. 2022

European Journal of Medicinal Chemistry

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Breakdown of chemo-immune resistance by a TDO2-targeted Pt(IV) prodrug via attenuating endogenous Kyn-AhR-AQP4 metabolic circuity and TLS-promoted genomic instability

Cited by 8 publications

References 49 publications

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

Pancancer Analysis of Revealed TDO2 as a Biomarker of Prognosis and Immunotherapy

The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer

The role of Platinum(IV)-based antitumor drugs and the anticancer immune response in medicinal inorganic chemistry. A systematic review from 2017 to 2022

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