[P-12] Integrating analysis of the expression of IDO1 and TDO2 in bladder cancer

Thanh Tu Nguyen, Quoc Thang Pham, Thao Quyen Nguyen, Duc Tung Luu, Thi Nhu Diem Pham, Thi Thanh Tam Bui, Thanh Tu Duong, Dang Anh Thu Phan, and Quoc Dat Ngo

Department of Pathology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam


Background and Objectives: 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.

Materials and Methods: 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 download 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/.

Results: We figured out the overexpression of IDO1 and TDO2 in basal type compared with other molecular subtypes in BLCA. P53 and RB1 mutations were associated with upregulation of IDO1 and TDO2 expression whereas FGFR3 mutation was associated with downregulation of IDO1 and TDO2 expression.  IDO1 and TDO2 expression were significantly correlated with purity and immune cell infiltrates, including CD8+ - T cells, CD4+ - T cells, B cells, neutrophils and macrophages as wells as myeloid dendritic cells. Interestingly, TDO2 were positively correlated with cancer-associated fibroblasts (CAFs) (ρ = 0.5, p = 1.14 x 10-24). PD-L1 expression was also correlated with IDO1 (ρ = 0.64, p = 4.42 x 10-49) and TDO2 expression (ρ = 0.42, p = 5.01 x 10-19).

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