2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.11B.07 Choline Metabolism Reprogramming Mediates an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer

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Lung cancer remains one of the most common malignancies worldwide, and while immunotherapy has significantly transformed its treatment, not all patients benefit. Many present either primary or secondary resistance, resulting in poor outcomes and survival rates. Identifying accurate biomarkers and understanding the resistance mechanisms to immunotherapy is crucial.<br /><br />This study focused on the potential of cholinesterase (ChE) activity and choline metabolism as predictive biomarkers for immunotherapy response in advanced non-small cell lung cancer (NSCLC). Abnormal ChE activity and enhanced choline metabolism have been linked with cancer progression and poor prognosis. However, their exact role in lung cancer's response to immunotherapy is not well understood. <br /><br />Involving 277 advanced NSCLC patients receiving first-line immunotherapy, the study found that elevated baseline ChE levels were associated with significantly longer progression-free survival (PFS) and overall survival (OS). Patients with higher ChE levels showed improved survival metrics compared to those with lower ChE levels. Moreover, an increase in ChE levels during treatment correlated with better PFS and OS, suggesting ChE is a valuable marker for predicting immunotherapy benefit.<br /><br />Additionally, choline metabolism-related genes, including MTHFD1, were explored. MTHFD1's overexpression was closely linked with tumor-associated macrophages (TAMs), indicating its role in creating an immunosuppressive microenvironment conducive to tumor progression. The study established a prognostic signature based on these genes, correlating them with immune evasion and metabolic reprogramming.<br /><br />A constructed nomogram based on ChE levels and other clinical factors effectively stratified patients into different risk categories, offering predictive insights into survival outcomes. The signature and associated analyses underscore the potential of targeting choline metabolism and related pathways as therapeutic strategies to counter immunotherapy resistance in NSCLC.

Asset Subtitle

Yan HUANG

Meta Tag

Speaker Yan HUANG

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

lung cancer

immunotherapy

biomarkers

cholinesterase activity

choline metabolism

non-small cell lung cancer

progression-free survival

overall survival

tumor-associated macrophages

immunotherapy resistance