2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03C.03 Development of a Novel Immunotherapy for ICI Resistant KRAS-Mutantlung Cancer

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The study detailed in the document focuses on developing a novel immunotherapy for KRAS-mutant lung cancers, which are resistant to immune checkpoint inhibitors (ICIs). These cancers can be classified into two types based on mutations: KL (co-existing with LKB1 mutation) and KP (co-existing with TP53 mutation). ICIs have proven to be less effective for KL lung cancers compared to KP. <br /><br />The researchers aimed to identify new therapeutic targets for ICI-resistant KRAS-mutant lung cancers. They analyzed gene expression differences between KL and KP types using data from TCGA and CCLE, identifying a specific gene, referred to as "Gene X," whose expression was notably reduced in KL lung cancers.<br /><br />The study examined the function of "Protein X" through several methods:<br />1. Immunohistochemistry (IHC) staining of Protein X and LKB1 in clinical samples.<br />2. Co-culturing KL cancer cells with NK92 immune cells, assessing differences between groups with Protein X overexpression versus a control group.<br />3. An in vivo syngeneic tumor transplantation model using immunocompetent mice.<br /><br />Results confirmed that Protein X expression is reduced in KL lung cancers. The findings suggest that overexpressing Protein X could enhance the immunogenicity of KRAS-mutant lung cancers, potentially improving treatment effectiveness. The suggested further steps include investigating the detailed function of Protein X and validating its potential as a biomarker for immunotherapy in KRAS-mutant lung cancers using clinical data.<br /><br />These discoveries could lead to new therapeutic approaches and enhance the effectiveness of immunotherapy for KRAS-mutant lung cancers that are resistant to current ICI treatments.

Asset Subtitle

Toshiyuki Tenma

Meta Tag

Speaker Toshiyuki Tenma

Topic Tumor Biology – Translational Biology

Keywords

KRAS-mutant lung cancer

immunotherapy

immune checkpoint inhibitors

KL lung cancer

KP lung cancer

Gene X

Protein X

LKB1 mutation

TP53 mutation

therapeutic targets