2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - ePosters-EP01.05: Evaluating therapeutic marker expression and EMT heterogeneity in circulating tumor cells from SCLC liquid biopsies using mass cytometry

EP01.05: Evaluating therapeutic marker expression and EMT heterogeneity in circulating tumor cells from SCLC liquid biopsies using mass cytometry

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This study investigates the utility of mass cytometry (CyTOF) for analyzing circulating tumor cells (CTCs) in liquid biopsies from patients with Small Cell Lung Cancer (SCLC). Traditional tissue biopsies can be challenging due to tumor inaccessibility and patient health, so liquid biopsies offer a non-invasive alternative to study tumor dynamics in real-time. Despite the potential of CTCs for biomarker analyses in SCLC, they are seldom examined at single-cell resolution, a gap this study aims to address.<br /><br />Using CyTOF, the researchers performed deep phenotyping of CTCs directly from SCLC patient liquid biopsies. They identified CTCs based on negative CD45 and positive CD56 expression, further confirmed by TTF1 positivity. The study optimized a 20-marker antibody panel for CyTOF analysis, which revealed higher expression of SCLC subtype-specific transcription factors, CD24, and DLL3 in patient CTCs compared to healthy donors.<br /><br />The study successfully identified the four established SCLC subtypes within the CTCs, showcasing high heterogeneity in epithelial-mesenchymal transition (EMT) states, which requires further study. Significantly, the analysis observed a shift towards a more mesenchymal phenotype in CTCs from treatment-naïve to the treated/relapsed patient group, which may signal adaptive resistance mechanisms.<br /><br />The longitudinal tracking of patients, especially those undergoing tarlatamab treatment, indicated significant upregulation of CD24, potentially implicating it in resistance to anti-DLL3 therapy. This research marks the first use of CyTOF for single-cell proteomic profiling of CTCs in SCLC, highlighting its potential for real-time monitoring of disease progression and therapy response. It suggests that CyTOF could advance personalized medicine by enabling detailed phenotypic mapping of EMT and drug resistance states, offering insights into therapy response and resistance mechanisms.

Asset Subtitle

Mukulika Bose

Keywords

mass cytometry

CyTOF

circulating tumor cells

liquid biopsies

Small Cell Lung Cancer

SCLC

biomarker analyses

epithelial-mesenchymal transition

tarlatamab treatment

personalized medicine