2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.03 Artemisinin Enhances Anti-Tumor Immunity by Increasing FGL1 Ubiquitination Degradation via Activating TRIM21 In NSCLC

P1.03D.03 Artemisinin Enhances Anti-Tumor Immunity by Increasing FGL1 Ubiquitination Degradation via Activating TRIM21 In NSCLC

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The study investigates how artemisinin, a compound traditionally used to treat malaria, can enhance anti-tumor immunity in non-small cell lung cancer (NSCLC) by promoting the degradation of fibrinogen-like protein-1 (FGL1) via the activation of tripartite motif 21 (TRIM21), a ubiquitin ligase. The research reveals that high expression of FGL1 in NSCLC is associated with poor prognosis in immunotherapy, but its endogenous degradation pathway was previously unclear.<br /><br />To explore this, the study utilized subcutaneous tumor models of NSCLC in both immunocompetent and immunodeficient mice, examining immune ligands in the tumor microenvironment. Techniques like immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (co-IP) helped identify and validate TRIM21 as a potential FGL1 ubiquitin ligase.<br /><br />Results showed artemisinin inhibited tumor progression in immunocompetent mice, suggesting that its effects rely on immune system interaction. Artemisinin increased the proliferation and activity of CD8 T cells, reducing FGL1 levels at the protein level, although mRNA levels remained unchanged. Further studies revealed TRIM21 interacts with FGL1, catalyzing its ubiquitination at specific lysine sites, which leads to protein degradation. This degradation process reduces FGL1's immunosuppressive effect, thereby enhancing the immune system’s ability to destroy tumor cells.<br /><br />Moreover, clinical cohort analyses indicated a negative correlation between FGL1 and TRIM21, with their relative levels linked to patient prognosis. Combining artemisinin with anti-PD-1 immunotherapy in mice improved the activation of CD8 T cells and overall treatment efficacy, indicating a promising therapeutic strategy.<br /><br />In conclusion, artemisinin may boost anti-tumor immunity in NSCLC by enhancing FGL1 degradation through TRIM21 activation, offering a novel approach to improve immunotherapy outcomes.

Asset Subtitle

Yuchen Zhang

Meta Tag

Speaker Yuchen Zhang

Topic Tumor Biology – Translational Biology

Keywords

artemisinin

non-small cell lung cancer

FGL1 degradation

TRIM21

immunotherapy

CD8 T cells

ubiquitination

tumor microenvironment

anti-PD-1 therapy

immune system interaction