Jul 22, 2016 · Loss of Cdk5 results in persistent expression of the PD-L1 transcriptional repressors, the interferon regulatory factors IRF2 and IRF2BP2, which likely leads to reduced PD-L1 expression on tumors. Our finding highlights a central role for Cdk5 in immune checkpoint regulation by tumor cells.

CDK5/PD-L1 signaling pathway is clinically prognostic. To elucidate the clinical relevance of CDK5, PD-L1, and PD-L1 T290 phosphorylation in HCC, immunohistochemical staining was performed on 88 HCC samples to determine their expression.

Nov 24, 2023 · Targeting CDK5 can synergize with PD-1 blockade to suppress HCC growth, which may have clinical benefits. Our study reveals a unique regulation of the degradation of PD-L1 in HCC, and provides an attractive therapeutic target, a potential drug, and a new prognostic marker for the clinical treatment …

In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered.

Within the immune system, CDK5 has been implicated in IFNγ-induced programmed death ligand 1 (PD-L1) upregulation, which allows certain cells to evade detection by the immune system. Decreased CDK5 expression led to increased expression of the PD-L1 transcriptional repressors IRF2 and IRF2BP and consequent decreased PD-L1 expression (Figure 2 ...

Loss of Cdk5 results in persistent expression of the PD-L1 transcriptional repressors, the interferon regulatory factors IRF2 and IRF2BP2, which likely leads to reduced PD-L1 expression on tumors.

In this study, we found that CDK5 phosphorylated PD- L1 at T290 to promote its interaction with chaperon protein heat- shock cognate protein 70 (HSC70) and degradation through chaperon- mediated autophagy (CMA).

Feb 1, 2020 · To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells via specifically knocking out Cyclin-dependent kinase 5 (Cdk5) gene in vivo.

FBXO22, a known ubiquitin E3 ligase, decreases the level of PD-L1 in NSCLC cells and increases their sensitivity to DNA-damaging therapies. Furthermore, targeting cyclin-dependent kinase 5 (CDK5), which is highly expressed in NSCLC, increases FBXO22 levels, leading to decreased expression of PD-L1.

Cyclin-dependent kinase (CDK5) phosphorylates PD-L1 at T290 and promotes the interaction between PD-L1 and HSC70, which facilitates PD-L1 degradation through chaperon-mediated autophagy. Upregulation of PD-L1 by CDK5 inhibitor PNU112455A improves the efficacy of anti-PD-1 therapy in preclinical hepatocellular carcinoma models.