2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.09 Noninvasive Blood Biopsy of CRTAM-Type 3 Immune Axis Enables Dynamic Monitoring of Iraes Over the Course of Immunotherapy in Lung Cancer

P1.06B.09 Noninvasive Blood Biopsy of CRTAM-Type 3 Immune Axis Enables Dynamic Monitoring of Iraes Over the Course of Immunotherapy in Lung Cancer

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The study explores the potential of using a noninvasive blood biopsy focused on the CRTAM-type 3 immune axis to dynamically monitor immune-related adverse events (irAEs) during immunotherapy in non-small cell lung cancer (NSCLC). Immune checkpoint blockade (ICB) is the primary treatment option for NSCLC lacking driver mutations. However, while effective against tumors, ICB often results in irAEs, which can lead to therapy withdrawal, decreased quality of life, or even patient fatalities, underscoring the need for a reliable biomarker to forecast these adverse events.<br /><br />The research employs preclinical models to simulate ICB-induced colitis, pneumonitis, and myocarditis, and utilizes RNA-sequencing to identify differential gene expressions. The study finds that CRTAM serves as a consistent biomarker across different irAE models. Crtam knockout mice demonstrated milder irAE symptoms compared to normal Crtam mice, suggesting a crucial role of CRTAM in irAE development. Furthermore, transcription factor analysis indicated a reduced expression of type 3 immune transcription factors in these knockout mice, supporting CRTAM's involvement in the immune response.<br /><br />Clinical evaluations were conducted on both in-house and external NSCLC patient cohorts. The in-house cohort revealed an elevation in plasma interleukin-17 (IL-17) and CRTAM expression on T cells in subjects experiencing irAEs compared to those who did not. The external cohort's plasma proteomics reinforced these findings, showing increased CRTAM and type 3 immune cytokines (IL-1 and IL-6) in baseline samples from patients who later developed irAEs.<br /><br />Conclusively, the blood biopsy method focusing on the CRTAM-type 3 immune axis shows promise for noninvasively monitoring the onset and progression of irAEs in NSCLC patients undergoing immunotherapy, potentially improving management and outcomes.

Asset Subtitle

Si-Cong Ma

Meta Tag

Speaker Si-Cong Ma

Topic Pathology & Biomarkers

Keywords

noninvasive blood biopsy

CRTAM-type 3 immune axis

immune-related adverse events

immunotherapy

non-small cell lung cancer

immune checkpoint blockade

biomarker

RNA-sequencing

interleukin-17

plasma proteomics