Abstract 5884: Comprehensive analyzing the expression of IDO1 and TDO2 in bladder cancer

Abstract Background: Several lines of evidence have been focused on the roles of tryptophan metabolism genes like indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) in bladder cancer progression. However, the alternative way of targeting in cancer immunotherapy has been not yet investigated in bladder cancer. Method: We explored and validated the clinicopathological significance and the correlation with immune infiltrates of IDO1 and TDO2 expression in bladder cancer using Bladder urothelial carcinoma (BLCA) and other Gene Expression Omnibus (GEO) datasets (GSE13570, GSE31684, GSE48277) downloaded from https://xenabrowser.net/ and https://www.ncbi.nlm.nih.gov/geo/. The correlation between IDO1, TDO2 expression and the immune infiltrates as well as PD-L1 gene expression in BLCA dataset was explored with TIMER2.0, http://timer.comp-genomics.org/. Immunohistochemistry was performed to validate the relationship between TDO2 and PD-L1 expression in bladder cancer. Results: We figured out the IDO1 and TDO2 expressions were significantly upregulated in basal type compared with other molecular subtypes in BLCA. P53 mutations were associated with upregulation of IDO1 and TDO2 expression (p<0.01) whereas FGFR3 mutation was associated with downregulation of IDO1 and TDO2 expression (p<0.001). The overexpression of IDO1, TDO2 overexpression was significantly associated with advanced disease in BC. IDO1 and TDO2 expression were significantly correlated with purity and immune cell infiltrates, including T cells CD8+, T cells CD4+, B cells, neutrophils, and macrophages as wells as myeloid dendritic cells. Interestingly, TDO2 were positively correlated with cancer-associated fibroblasts (CAFs) (rho=0.5, p=1.14e-24). PD-L1 expression was also correlated with IDO1 (rho=0.64, p=4.42e-49) and TDO2 expression (rho=0.42, p=5.01e-19). Immunohistochemistry revealed the correlation between TDO2 and PD-L1 expression (p=0.011). Conclusion: 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. Citation Format: Quoc Thang Pham, Thanh Tu Nguyen, Thao Quyen Nguyen, Duc Tung Luu, Thi Nhu Diem Pham, Thi Thanh Tam Bui, Thanh Tu Duong, Dang Anh Thu Phan, Quoc Dat Ngo. Comprehensive analyzing the expression of IDO1 and TDO2 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5884.