2023 World Conference on Lung Cancer (Posters)-P1.04. CDK4/6 Inhibitor Improves Radioimmunotherapy Efficacy via Inducing PD-L1 Transcription through Increased c-Jun Activation in NSCLC

P1.04. CDK4/6 Inhibitor Improves Radioimmunotherapy Efficacy via Inducing PD-L1 Transcription through Increased c-Jun Activation in NSCLC - PDF(Slides)

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A study conducted by researchers from Zhongnan Hospital of Wuhan University in China has found that combining a CDK4/6 inhibitor with radioimmunotherapy can effectively suppress tumor growth in non-small cell lung cancer (NSCLC). The researchers discovered that CDK4/6 inhibition, when combined with radiation, upregulated the expression of PD-L1, a protein found on the surface of cancer cells that suppresses the immune system's ability to attack tumors. This upregulation of PD-L1 was found to be mediated by increased activation of the c-Jun protein. <br /><br />Further experiments showed that treatment with the CDK4/6 inhibitor abemaciclib improved the inhibitory effects of radiation and PD-1 blockade on NSCLC growth in mice. This was accompanied by increased infiltration of CD8 T cells, which play a crucial role in immune response against cancer cells. The researchers also observed that abemaciclib synergistically upregulated PD-L1 expression in combination with radiation, both in tumors and NSCLC cells in vitro.<br /><br />The study further demonstrated that abemaciclib induced phosphorylation of c-Jun, leading to the upregulation of PD-L1 transcription. Knockdown of c-Jun or inhibition of the JNK pathway resulted in decreased PD-L1 expression. The combination of abemaciclib and radiation also increased c-Jun phosphorylation.<br /><br />These findings suggest that abemaciclib can enhance the efficacy of radioimmunotherapy in NSCLC by increasing PD-L1 expression through the activation of the c-Jun pathway. This novel strategy provides a potential approach for the treatment of NSCLC, with abemaciclib acting as a synergistic agent to improve the therapeutic outcomes of radioimmunotherapy.

Asset Subtitle

Yan Gong

Meta Tag

Speaker Yan Gong

Topic Tumor Biology: Preclinical Biology - Radiobiology

Keywords

CDK4/6 inhibitor

radioimmunotherapy

tumor growth

non-small cell lung cancer

NSCLC

PD-L1 upregulation

c-Jun protein

abemaciclib

CD8 T cells

PD-L1 expression