Effects of CRISPR-Cas9-mediated CEP55 gene knockout on immune evasion mechanisms of liver cancer cells

Apr 8, 2026Scientific reports

How removing the CEP55 gene with CRISPR-Cas9 affects liver cancer cells’ ability to avoid the immune system

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Abstract

CEP55 knockout significantly reduced PD-L1 expression while upregulating MHC class I levels.

Deletion of CEP55 in liver cancer cells is associated with enhanced tumor immunogenicity.
CEP55 knockout attenuates the activation of a specific immune signaling pathway under certain conditions.
Reduced levels of reactive oxygen species and immunosuppressive cytokines were observed following CEP55 deletion.
Inhibition of tumor cell migration and invasion, along with increased apoptosis, was noted in CEP55-deficient cells.
Enhanced T cell activity, including increased secretion of key cytokines, was observed when T cells interacted with CEP55 knockout cells.

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This study investigates the role of centrosomal protein CEP55 in immune evasion by liver cancer cells and evaluates the effects of its knockout using CRISPR-Cas9 technology. CEP55-knockout models were established in human hepatocellular carcinoma cell lines Huh7 and HepG2, and alterations in immune-related molecules, tumor cell behavior, and antitumor immune responses were systematically assessed. CEP55 knockout significantly reduced PD-L1 expression while upregulating MHC class I levels, thereby enhancing tumor immunogenicity. Mechanistically, CEP55 deletion attenuated STAT1 activation, particularly under interferon-γ (IFN-γ) stimulation, suggesting involvement of the IFN-γ-STAT1 signaling axis in CEP55-mediated immune regulation. In parallel, CEP55 knockout markedly decreased intracellular reactive oxygen species (ROS) levels and suppressed the secretion of immunosuppressive cytokines IL-10 and TGF-β, indicating remodeling of the immunosuppressive tumor microenvironment. Functional assays demonstrated that CEP55 deficiency inhibited tumor cell migration and invasion and promoted apoptosis. Importantly, co-culture experiments revealed that CEP55 knockout enhanced T cell effector function, as evidenced by increased secretion of IFN-γ and Granzyme B and restored T cell-mediated cytotoxicity, even in the presence of IFN-γ stimulation. Collectively, these findings indicate that CEP55 promotes liver cancer immune escape and malignant progression through modulation of STAT1-dependent PD-L1/MHC-I expression, oxidative stress, and immunosuppressive signaling. Targeting CEP55 may therefore represent a potential strategy to improve antitumor immune recognition in liver cancer.

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Effects of CRISPR-Cas9-mediated CEP55 gene knockout on immune evasion mechanisms of liver cancer cells

Abstract

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