2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP02.56

PP02.56 - Jinbo Zhao

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Lung cancer remains the leading cause of cancer-related morbidity and mortality, with early-stage lung adenocarcinoma (LUAD), particularly stage I characterized by a tumor size of 3 cm or less and no metastasis (T1N0M0), having a relatively high cure rate. However, clinical research indicates that approximately 30% of stage T1 lung adenocarcinoma cases may progress to involve mediastinal lymph nodes (N2) and even distant organs (M1) metastasis, although the underlying mechanism behind this progression is not clearly understood.<br /><br />A study explored the metastatic mechanisms and potential therapeutic targets for T1N2M0 lung adenocarcinoma by analyzing three cases of T1N0M0 and T1N2M0 LUAD along with their metastatic lymph nodes using single-cell sequencing. The research established lung adenocarcinoma cell lines with genetic alterations such as TPX2 and PBK gene knockouts and overexpressions. Researchers used a variety of experimental models including subcutaneous tumor-bearing nude mice, patient-derived xenograft (PDX) models, and humanized immune mouse models to investigate the effects of targeting these genes with AAV9 vectors.<br /><br />Results showed that TPX2()PBK() cells play a significant role in mediating N2 lymph node metastasis and altering the immune microenvironment of LUAD, promoting immune escape through CD147 interaction. The study suggests that targeting TPX2 and PBK genes through AAV6 and AAV9 vectors holds promise and may serve as a novel gene therapy approach to inhibit N2 lymph node metastasis in early-stage lung adenocarcinoma. The study was supported by several foundations including the Shaanxi Outstanding Youth Natural Science Foundation and the National Natural Science Foundation of China.

Keywords

lung cancer

adenocarcinoma

metastasis

TPX2 gene

PBK gene

single-cell sequencing

immune escape

gene therapy

AAV9 vectors

lymph nodes