The IDO1 Knockout UM-UC-3 Polyclonal Cells represent a robust CRISPR/Cas9-edited polyclonal cell population in which the human IDO1 gene has been disrupted to generate a loss-of-function model. This product is derived from the UM-UC-3 urothelial carcinoma cell line and is supplied as a heterogeneous pool of knockout cells, eliminating the need for single-cell cloning. The polyclonal format preserves population-level heterogeneity while ensuring target-gene disruption, making it suitable for studying IDO1-dependent immunoregulatory mechanisms in a tumor context.
The UM-UC-3 cell line, derived from a primary transitional cell carcinoma of the male urinary bladder, serves as a well-characterized model for high-grade bladder cancer. These adherent epithelial cells maintain key tumor characteristics and are widely used to investigate oncogenic signaling, drug resistance, and tumor-immune crosstalk. Their clinical relevance makes them an ideal host for studying the role of IDO1 in tumor immune evasion.
IDO1 encodes indoleamine 2,3-dioxygenase 1, a heme-containing enzyme that catalyzes tryptophan conversion to kynurenine in the rate-limiting step of the kynurenine pathway. Its expression is strongly induced by interferon-gamma (IFNG) through JAK1/2-STAT1 signaling, with STAT1 and IRF1 acting as key transcription factors, and additional regulation by NF-??B and IL-6. Kynurenine activates the aryl hydrocarbon receptor (AhR) and, together with GCN2-mediated amino acid sensing, promotes T-cell anergy and tolerance. SOCS3 ubiquitinates IDO1, while IL-4R?? modulates its signaling. Disruption of IDO1 abolishes kynurenine production, blocking AhR and GCN2-dependent pathways that normally suppress T-cell proliferation and function.
In the bladder tumor microenvironment, IDO1-driven tryptophan depletion and kynurenine accumulation foster immunosuppression, aiding immune evasion and resistance to therapy. The IDO1 Knockout UM-UC-3 Polyclonal Cells offer a physiologically relevant platform to dissect how loss of IDO1 alters metabolic and immune checkpoints in urothelial carcinoma. They enable investigation of compensatory immunosuppressive mechanisms and crosstalk with other immunomodulatory pathways, providing insights into combination strategies to enhance anti-tumor immunity.
These knockout cells are a versatile resource for immuno-oncology and tumor microenvironment research, enabling studies on IDO1-mediated T-cell suppression, AhR signaling, and tryptophan metabolism. Typical applications include kynurenine quantification (HPLC or colorimetric), western blotting, RT-qPCR, T-cell proliferation assays with peripheral blood mononuclear cells, and flow cytometric analysis of CD8+ T-cell activation. The model also supports IDO1 inhibitor screening and AhR reporter assays. For further technical details, contact Ascent Research.
