The IDO1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-mediated polyclonal knockout population derived from the human 786-O renal cell adenocarcinoma line. This product features a heterogeneous pool of cells with targeted disruption of the IDO1 gene, encoding indoleamine 2,3-dioxygenase 1. As polyclonal knockout cells, they provide a population-level loss-of-function model without clonal selection, suitable for direct experimental use.
The 786-O cell line originates from a clear cell renal cell carcinoma and carries a VHL mutation, leading to constitutive HIF stabilization and a pseudohypoxic phenotype. This background is invaluable for studying kidney cancer pathogenesis, including angiogenesis and metabolic adaptation. The VHL deficiency also shapes the tumor microenvironment, offering a relevant context for immune evasion research.
IDO1 catalyzes the conversion of L-tryptophan to kynurenine, consuming oxygen and requiring heme as a cofactor. Its expression is induced by IFNG and IFNA via STAT1/IRF1 signaling, and modulated by TNF, IL1B, TGFB1, and immune checkpoint signals (CTLA4, PDCD1). The resulting tryptophan depletion and kynurenine accumulation activate the aryl hydrocarbon receptor (AHR), promoting FOXP3+ regulatory T cell differentiation and inhibiting mTORC1-dependent effector T cell functions. Downstream enzymes like TDO2, KMO, KYNU, HAAO, and QPRT extend the pathway.
In 786-O cells, IDO1-driven tryptophan catabolism contributes to an immunosuppressive niche, aiding tumor immune evasion. IDO1 knockout abrogates this process, enabling investigation of restored anti-tumor immunity. The VHL-mutant background may intersect with IDO1 signaling, making this model valuable for dissecting metabolic and immune checkpoint interactions in renal cancer.
Applications include co-culture assays to measure T cell proliferation, kynurenine quantification via HPLC, and flow cytometry for Treg markers (FOXP3). The model facilitates studies in cancer immunotherapy, immune tolerance, and neuroinflammation, and can be integrated with transcriptomic or proteomic approaches. For inquiries, contact Ascent Research.
