The IL27 Knockout 786-O Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population targeting the IL27 gene in Homo sapiens 786-O clear cell renal cell carcinoma cells. This loss-of-function model is designed for investigating IL27, a heterodimeric cytokine, in tumor biology and immune modulation, offering a VHL-deficient renal cancer background for signaling studies.
The 786-O cell line, derived from a primary clear cell adenocarcinoma of the kidney, serves as a well-established model of VHL-deficient renal epithelial carcinoma. Loss of VHL function results in constitutive hypoxia-inducible factor stabilization, mimicking oncogenic metabolic and angiogenic signatures often observed in renal tumors. These epithelial cells are widely applied to explore cancer cell signaling, drug responses, and interactions with the immune system.
IL27 functions as a heterodimer of IL27A and EBI3, signaling via a receptor complex comprising IL27RA (WSX-1) and gp130. Upon ligand binding, the receptor activates JAK1 and JAK2, leading to phosphorylation of STAT1 and STAT3, with additional engagement of MAPK and PI3K-AKT pathways. Expression of IL27 is stimulated by TLR4 ligands, IFN-gamma, CD40 ligation, and LPS. Downstream, STAT1 and STAT3 transcriptionally regulate targets including T-bet, IL-10, and SOCS3, thereby orchestrating Th1 differentiation and regulatory T cell induction. This positions IL27 as a cytokine with dual pro- and anti-inflammatory functions.
In the 786-O clear cell renal carcinoma context, IL27 signaling may modulate immune responses within the tumor microenvironment. The VHL-deficient background of these cells allows interrogation of crosstalk between IL27-driven JAK-STAT pathways and hypoxia-associated signaling networks. Disruption of IL27 in this model facilitates examination of mechanisms governing Th1/regulatory T cell balance, which can influence anti-tumor immunity and immune evasion. Such studies are relevant for understanding renal cancer progression and optimizing immunotherapy strategies.
Typical applications include western blotting for phospho-STAT1/STAT3, RT-qPCR analysis of SOCS3 and IL-10 transcripts, and ELISA for IFN-gamma secretion. Flow cytometry can assess immune checkpoint markers, while T cell co-culture experiments probe tumor-immune interactions. Proliferation and drug sensitivity assays further enable identification of IL27-dependent vulnerabilities in renal cancer. For further technical details, contact Ascent Research.
