The KLRB1 Knockout PaTu 8988t Polyclonal Cells consist of a heterogeneous CRISPR/Cas9-edited population of PaTu 8988t cells carrying targeted disruption of the KLRB1 gene. This polyclonal format provides a loss-of-function model suitable for studying CD161 receptor biology without the biases of clonal selection. The knockout product allows functional interrogation of KLRB1-dependent signaling within a human pancreatic cancer background.
The PaTu 8988t cell line is a human pancreatic ductal adenocarcinoma (PDAC) epithelial cell line derived from a liver metastasis. It harbors oncogenic KRAS G12V and p53 mutations, recapitulating aggressive tumor genetics. This line is extensively used in cancer research for investigating tumor proliferation, drug resistance, and metastatic mechanisms. Its epithelial character makes it a relevant model for exploring tumor-intrinsic immune modulator expression and its impact on the PDAC microenvironment.
KLRB1 encodes the inhibitory receptor CD161, which features an ITIM domain. Binding to its ligand LLT1 (CLEC2D) triggers recruitment of SHP-1 and SHP-2 phosphatases, leading to negative regulation of Vav-1 and PLC??. This cascade dampens NK cell cytotoxicity and cytokine production, acting as an immune checkpoint. Upstream, CD161 expression is induced by IL-12, IL-15, and transcription factors T-bet and Eomes. Downstream consequences include NFAT inhibition and suppression of the MAPK/ERK pathway. Through these interactions, CD161 modulates both adaptive and innate immune responses and may contribute to tumor immune evasion when engaged by LLT1-expressing cells.
In PaTu 8988t pancreatic cancer cells, KLRB1 knockout allows researchers to examine whether CD161 influences tumor cell-intrinsic signaling or alters tumor?Cimmune interactions. Given the presence of SHP-1/SHP-2 and potential LLT1 expression, CD161 disruption may impact basal signaling or response to immune effector engagement. The polyclonal knockout population mirrors the genetic heterogeneity of cancer, enabling studies of migration, invasion, and susceptibility to NK cell-mediated cytotoxicity. This model is valuable for dissecting CD161??s role in PDAC progression and for evaluating targeted therapeutic strategies aimed at the CD161?CLLT1 axis.
Typical applications include western blotting and RT-qPCR to verify KLRB1 disruption, flow cytometry for CD161 surface expression, and functional assays such as cell viability, proliferation, and transwell migration/invasion. Co-culture with immune cells quantifies NK cell killing and cytokine output, directly testing CD161??s checkpoint function. The model also enables pharmacological screening for modulators of CD161 signaling and downstream effectors like SHP-1/SHP-2 and MAPK/ERK. For technical inquiries or custom requirements, please contact Ascent Research.
