The IL27RA Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma epithelial cell line. This product comprises a heterogeneous pool of cells harboring targeted disruption of the IL27RA gene, encoding the alpha subunit of the interleukin-27 receptor. The polyclonal format provides a genetically diverse loss-of-function model that avoids single-cell clonal artifacts, enabling robust investigation of IL-27 receptor signaling in a cancer-relevant context.
The parental NCI-H1975 cell line is a widely used in vitro model of non-small cell lung cancer, established from pleural effusion of a patient with lung adenocarcinoma. It carries an activating EGFR L858R mutation and the secondary T790M resistance mutation, alongside loss of PTEN function and a p53 mutation. These genetic lesions drive oncogenic signaling, genomic instability, and altered apoptosis, making the line particularly valuable for studying tumor progression, drug resistance, and immune evasion.
IL27RA forms a heterodimeric receptor complex with IL6ST (gp130) upon binding interleukin-27 (IL-27; p28/EBI3 heterodimer). Ligand engagement activates JAK1 and JAK2, leading to phosphorylation of STAT1 and STAT3 transcription factors. Activated STATs induce expression of T-bet (TBX21), IL-10, SOCS1, and PD-L1 (CD274), while SOCS1 and SOCS3 mediate negative feedback. Through these effectors, IL27RA modulates Th1 differentiation, inflammatory responses, and anti-tumor immunity, bridging adaptive immunity and tumor pathogenesis.
In the EGFR-mutant NCI-H1975 background, IL-27 signaling influences the tumor immune microenvironment and therapy sensitivity. Disruption of IL27RA allows dissection of IL-27-dependent, STAT3-driven PD-L1 expression linked to immune checkpoint escape. The concurrent PTEN and p53 mutations provide a physiologically relevant platform to study oncogenic-immune crosstalk, making this model suitable for exploring how IL-27 affects cell-intrinsic signaling and immune cell interactions in lung adenocarcinoma.
These polyclonal knockout cells support diverse experimental applications. IL-27 stimulation followed by phospho-kinase profiling or western blotting for pSTAT1/pSTAT3 enables comparative signal analysis. Flow cytometry confirms loss of surface IL27RA, and RT-qPCR quantifies targets like IL10 and SOCS1. STAT-driven luciferase reporters, apoptosis assays, and drug sensitivity screens provide functional readouts. Applications span tumor immunology, immune checkpoint regulation, and preclinical lung cancer therapeutic evaluation. For further technical consultation, please contact Ascent Research.
