IDO1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the AGS human gastric adenocarcinoma cell line. This product provides a loss-of-function model for the IDO1 gene, achieved through targeted gene disruption, allowing functional interrogation of IDO1-mediated immunoregulation in gastric cancer. The polyclonal format ensures a heterogeneous knockout population, suitable for bulk assays and representing a diverse genetic background.
The AGS parental cell line is a well-characterized human gastric adenocarcinoma epithelial cell line isolated from a female patient’s stomach tumor fragment. Adherent epithelial morphology and malignant transformation make AGS cells a widely used model for gastric cancer studies, including tumor cell biology, signal transduction, and host-immune interactions.
IDO1 encodes an immunoregulatory heme enzyme that catalyzes the rate-limiting step of L-tryptophan catabolism to N-formylkynurenine, initiating kynurenine pathway metabolism. Expression is rapidly induced by IFN-?? through JAK-STAT signaling, with STAT1 and IRF-1 acting as key transcription factors, and is further modulated by TNF-??, IL-1??, IL-6, TGF-??, and NF-??B. The resulting tryptophan depletion and kynurenine accumulation drive immunosuppression: kynurenine serves as an endogenous agonist of the aryl hydrocarbon receptor (AhR), promoting FoxP3+ regulatory T-cell differentiation, while GCN2 activation and mTORC1 inhibition mimic amino acid starvation, leading to effector T-cell dysfunction and apoptosis. Heme cofactor and proteasomal degradation further tune IDO1 activity, linking cytokine signals to metabolic immune regulation.
In AGS gastric adenocarcinoma cells, IDO1 expression contributes to an immunosuppressive tumor microenvironment by depleting tryptophan and secreting kynurenine, which suppresses local T-cell responses. This polyclonal knockout model disrupts that pathway, enabling researchers to dissect gastric cancer immune evasion mechanisms and evaluate the functional consequences of IDO1 loss on T-cell behavior, kynurenine production, and AhR-driven transcriptional programs. Co-culture of knockout AGS cells with human PBMCs provides a physiologically relevant system to assess T-cell proliferation and Treg induction.
Key applications include tumor immunology studies, IDO1 inhibitor evaluation, immune checkpoint combination therapy research, and biomarker discovery for immunotherapy. Representative assays employ this cell product for Western blotting and RT-qPCR analysis of IDO1 expression, HPLC-based kynurenine quantification, T-cell proliferation assays using conditioned medium, AhR luciferase reporter assays to monitor transcriptional activity, and flow cytometric enumeration of CD4+CD25+FoxP3+ regulatory T cells following co-culture. This IDO1 Knockout AGS Polyclonal Cell product is suitable for advanced gastric cancer research and drug discovery programs. For additional information or technical support, please contact Ascent Research.
