KLRB1 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human urinary bladder transitional cell carcinoma cell line UM-UC-3. This product provides a loss-of-function model for the KLRB1 gene, encoding the C-type lectin-like receptor CD161 (NKR-P1A). The polyclonal knockout pool results from CRISPR/Cas9-mediated gene disruption across a population of cells, offering heterogeneous but targeted inactivation of KLRB1 expression. It serves as a versatile tool for studying CD161-dependent signaling pathways in immune receptor biology and bladder cancer research.
The parental UM-UC-3 cell line originates from a human male bladder carcinoma and exhibits adherent epithelial morphology. As a model of urinary bladder transitional cell carcinoma, it retains key characteristics of bladder cancer pathophysiology, including aberrant signaling networks and immune evasion capabilities. The engineered knockout of KLRB1 in this background enables direct assessment of CD161 function in a relevant oncogenic context, facilitating studies on how this receptor modulates cancer cell behavior and immune recognition.
KLRB1 encodes CD161, which interacts with its cognate ligand LLT1 (CLEC2D) to transduce immunomodulatory signals. Upon ligand engagement, CD161 recruits the tyrosine phosphatases SHP-1 (PTPN6) and SHP-2 (PTPN11), initiating an inhibitory signaling cascade, and can also couple to activating pathways involving PI3K/AKT and ERK. The receptor is expressed on natural killer (NK) cells and T cell subsets, where it regulates cytotoxicity and cytokine secretion, including IFN-??, TNF-??, and IL-4. Upstream, KLRB1 expression is controlled by cytokines such as IL-12, IL-15, and IL-18, and transcription factors TCF7 and ZBTB7B. Downstream, CD161 signaling modulates the release of cytotoxic granules containing granzyme B and perforin.
In the context of UM-UC-3 bladder cancer cells, KLRB1 knockout disrupts CD161-mediated inhibitory signaling, potentially altering the secretion of immunomodulatory cytokines and affecting the tumor’s ability to evade immune surveillance. Since bladder cancers can express LLT1, the CD161-LLT1 axis may contribute to immune checkpoint-like interactions within the tumor microenvironment. Loss of CD161 in this cancer cell model provides a platform to dissect how tumor-intrinsic expression of this receptor influences immune cell crosstalk, particularly with NK cells and cytotoxic T lymphocytes.
Researchers can employ these polyclonal knockout cells in a wide array of applications, including immuno-oncology studies, tumor microenvironment profiling, and drug screening campaigns. Representative experimental approaches include flow cytometry to confirm CD161 ablation, Western blotting and RT-qPCR for expression analysis, and functional assays such as cytokine profiling via ELISA, cytotoxicity co-cultures with immune effector cells, and migration/invasion assays. The model is also suitable for drug sensitivity testing to identify compounds that exploit CD161 deficiency. By providing a robust in vitro platform, this product accelerates discovery in bladder cancer and immune checkpoint biology. For further technical details or custom inquiries, please contact Ascent Research.
