The IDO1 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human A2780 ovarian carcinoma cell line. This product represents a pooled loss-of-function model for indoleamine 2,3-dioxygenase 1 (IDO1), generated through targeted gene disruption without single-cell cloning, thereby preserving a heterogeneous editing landscape that mirrors population-level effects.
The A2780 cell line is an epithelial ovarian carcinoma model originally established from an untreated patient. It is widely utilized in ovarian cancer research due to its well-characterized growth behavior and sensitivity to platinum-based chemotherapeutics. A2780 cells maintain relevant molecular features of high-grade serous ovarian carcinoma, making them a suitable host for functional genomics, drug testing, and in vivo xenograft studies.
IDO1 encodes a heme-containing dioxygenase that catalyzes the first and rate-limiting step of tryptophan degradation via the kynurenine pathway. Transcriptionally induced by IFN-??, TNF-??, and IL-1?? through STAT1 and NF-??B signaling, IDO1 depletes local tryptophan and produces kynurenine, which acts as an endogenous agonist for the aryl hydrocarbon receptor (AhR). This signaling cascade promotes the differentiation and function of regulatory T cells (Tregs) while simultaneously suppressing effector T-cell responses through GCN2 kinase activation and mTOR inhibition. IDO1 further interacts with the phosphatases SHP-1 and SHP-2, linking tryptophan metabolism to broader immunomodulatory networks. Collectively, IDO1-driven metabolic remodeling facilitates immune tolerance and tumor immune evasion.
In the context of ovarian cancer, IDO1 is frequently overexpressed and contributes to an immunosuppressive tumor microenvironment. The A2780 cell line endogenously expresses IDO1 upon cytokine stimulation, mirroring clinical observations. Therefore, IDO1 knockout in A2780 provides a direct model to investigate how loss of tryptophan catabolism impacts kynurenine generation, AhR activation, and downstream T-cell suppression. This system enables dissection of IDO1-dependent immune evasion mechanisms specifically within a human ovarian carcinoma background, offering translational relevance for ovarian cancer immunotherapy.
These polyclonal knockout cells are suitable for a wide array of functional assays, including confirmation of IDO1 knockout by Western blotting and RT-qPCR, measurement of kynurenine-to-tryptophan ratios via LC-MS, T-cell proliferation assays in coculture systems, and flow cytometric analysis of immune checkpoint molecules. Researchers can employ the model to evaluate IDO1 inhibitors, explore combination strategies with anti-PD-1/PD-L1 therapies, and perform xenograft tumor growth studies to assess in vivo effects. For further information, please contact Ascent Research.
