2. Academic Validation
  3. Cyclin dependent kinase 9 inhibition reduced programmed death-ligand 1 expression and improved treatment efficacy in hepatocellular carcinoma

Cyclin dependent kinase 9 inhibition reduced programmed death-ligand 1 expression and improved treatment efficacy in hepatocellular carcinoma

  • Heliyon. 2024 Jul 8;10(14):e34289. doi: 10.1016/j.heliyon.2024.e34289.
Yu-Yun Shao 1 2 3,  Min-Shu Hsieh 4 5 6,  Yi-Hsuan Lee 4 5,  Hung-Wei Hsu 2,  Rita Robin Wo 2,  Han-Yu Wang 2,  Ann-Lii Cheng 1 7 2 3,  Chih-Hung Hsu 1 2 3
Affiliations

Affiliations

  • 1 Graduate Institute of Oncology, National Taiwan University College of Medicine, 1, Sec. 1, Ren'ai Rd., Taipei City, 10051, R.O.C, Taiwan.
  • 2 Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Road, Taipei City, 10002, R.O.C, Taiwan.
  • 3 Department of Medical Oncology, National Taiwan University Cancer Center, 57, Ln. 155, Sec. 3, Keelung Rd., Taipei City, 106, R.O.C, Taiwan.
  • 4 Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, 1, Sec. 1, Ren'ai Rd., Taipei City, 10051, R.O.C, Taiwan.
  • 5 Department of Pathology, National Taiwan University Hospital, 7, Chun-Shan S Road, Taipei City, 10002, R.O.C, Taiwan.
  • 6 Department of Pathology, National Taiwan University Cancer Center, 57, Ln. 155, Sec. 3, Keelung Rd., Taipei City, 106, R.O.C, Taiwan.
  • 7 Department of Internal Medicine, National Taiwan University College of Medicine, 1, Sec. 1, Ren'ai Rd., Taipei City, 10051, R.O.C, Taiwan.
PMID: 39100490 DOI: 10.1016/j.heliyon.2024.e34289
Abstract

The anti-programmed death-ligand 1 (PD-L1) antibody is a standard therapy for advanced hepatocellular carcinoma (HCC). Tumor expression of PD-L1 can be induced upon stimulus. Because cyclin-dependent kinase 9 (CDK9) inhibition reduces the expression of inducible proteins, we explored the influence of CDK9 inhibition on PD-L1 expression in HCC cells. We found that PD-L1 expression was low in HCC cells; however, IFN-γ treatment increased this expression. CDK9 inhibitors AZD4573 and atuveciclib reduced the IFN-γ induced PD-L1 expression in a dose-dependent manner. CDK9 knockdown yielded similar results, but CDK9 overexpression reversed the influence of the CDK9 inhibitors. In the orthotopic mouse model, mice treated with a CDK9 Inhibitor and an anti-PD-L1 antibody had significantly smaller tumors and exhibited longer survival than mice treated with either agent. In conclusion, CDK9 inhibition could reduce the expression of PD-L1 in HCC cells. Using both CDK9 inhibitors and anti-PD-L1 Antibodies is more effective than using either agent alone.

Keywords

Cyclin dependent kinase; Hepatocellular carcinoma; Immune checkpoint inhibitor; Immune checkpoints; PD-L1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112088
    99.98%, CDK9抑制剂
    CDK
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