2023 World Conference on Lung Cancer (Posters)-EP09.02. Fibrates Enhances Radiotherapy Efficacy by Elevating HDL Levels to Induce Tumor Cell Ferroptosis in NSCLC with Brain Metastasis

EP09.02. Fibrates Enhances Radiotherapy Efficacy by Elevating HDL Levels to Induce Tumor Cell Ferroptosis in NSCLC with Brain Metastasis - PDF(Abstract)

Back to course

Pdf Summary

This study investigates the relationship between lipid levels and the efficacy of radiotherapy in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). The researchers collected clinical information from 78 NSCLC BM patients and analyzed the relationship between blood lipids and the efficacy of brain radiotherapy. They found that NSCLC BM patients with elevated high-density lipoprotein (HDL) and normal cholesterol levels had longer progression-free survival (iPFS) and overall survival (OS). Non-targeted metabolomics assays showed that suppressed PPARα may cause abnormalities in HDL and cholesterol levels in BM patients. In vitro and in vivo experiments demonstrated that fenofibrate, a fibrate drug, promotes HDL synthesis and induces ionizing radiation-induced ferroptosis, thus enhancing the efficacy of radiotherapy. Lipidomic assays revealed that fenofibrate alters intracellular fatty acid composition, particularly polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs). Furthermore, TCR-seq analysis showed a positive correlation between HDL levels and T-cell diversity after brain radiotherapy. Combination treatment with fenofibrate and radiotherapy increased CD8 T cell infiltration within the tumor microenvironment and improved the efficacy of PD-1 monoclonal antibody immunotherapy. The researchers conclude that blood HDL and total cholesterol levels correlate with the efficacy of brain radiotherapy in NSCLC BM patients. Modulating HDL levels alters the composition of fatty acids in tumor cells and enhances radiotherapy-induced ferroptosis. Additionally, the combination of fenofibrate, radiotherapy, and immunotherapy may be a potential therapeutic strategy for NSCLC BM patients.

Asset Subtitle

Xiaorong Dong

Meta Tag

Speaker Xiaorong Dong

Topic Metastatic NSCLC: Local Therapies - Integration With Systemic Therapies

Keywords

lipid levels

radiotherapy efficacy

NSCLC patients

brain metastases

high-density lipoprotein

cholesterol levels

fenofibrate

ferroptosis

T-cell diversity

immunotherapy