2024 World Conference on Lung Cancer (WCLC) - Posters-P3.02G.03 High-Dose Ascorbic Acid Sensitizes Immunotherapy in LKB1-Deficient Lung Cancer by Promoting Tumor Cell Pyroptosis

P3.02G.03 High-Dose Ascorbic Acid Sensitizes Immunotherapy in LKB1-Deficient Lung Cancer by Promoting Tumor Cell Pyroptosis

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The study explores the potential of high-dose ascorbic acid (AA) to enhance the effectiveness of immunotherapy in treating LKB1-deficient lung cancer by inducing pyroptosis, a form of programmed cell death. LKB1-deficient cells usually show resistance to immune checkpoint blockade (ICB) treatments. The researchers established LKB1-deficient human lung cancer cell lines and murine lung cancer models to investigate the effects of high-dose AA.<br /><br />The study found that LKB1-deficient cancer cells exhibit a significant accumulation of reactive oxygen species (ROS) when treated with high-dose AA. These cells also absorb more AA due to the upregulation of the GLUT1 transporter. This redox imbalance triggers pyroptosis through the H2O2/ROS-Caspase-3-GSDME signaling pathway. The high dose of AA enhances the immune microenvironment, making it more favorable for immunotherapy by increasing the infiltration of beneficial T cells and reducing SPP1 macrophages that hinder immune responses.<br /><br />The research findings suggest that high-dose AA can reverse the resistance to anti-PD-1 therapy, commonly encountered in LKB1-deficient tumor treatments. This is achieved by promoting anti-tumor immune activities within the tumor immune microenvironment (TIME). This combination of high-dose AA and ICB could offer a promising new therapeutic strategy, although further clinical validation is needed.<br /><br />The study was supported by national and provincial science foundations in China and highlights the collaborative efforts in advancing lung cancer treatment strategies. The team expresses gratitude to various contributors, highlighting the importance of teamwork in scientific research.

Asset Subtitle

Xiaoting Cai

Meta Tag

Speaker Xiaoting Cai

Topic Tumor Biology – Preclinical Biology

Keywords

high-dose ascorbic acid

immunotherapy

LKB1-deficient lung cancer

pyroptosis

immune checkpoint blockade

reactive oxygen species

GLUT1 transporter

tumor immune microenvironment

anti-PD-1 therapy

lung cancer treatment