2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.04E.03 Enzymomics of Bodily Fluids Captures CD38-Orchestrated Immunometabolic Disorder for Early Detection of Immunotherapy Toxicity

EP.04E.03 Enzymomics of Bodily Fluids Captures CD38-Orchestrated Immunometabolic Disorder for Early Detection of Immunotherapy Toxicity

Back to course

Pdf Summary

The study explores the potential of "enzymomics," or the study of enzyme-related processes, to detect early signs of immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibition (ICI) therapy. These adverse events arise due to autoimmune responses triggered by the therapy. The research focuses on analyzing enzymatic activity in bodily fluids, such as bronchoalveolar lavage fluids (BALFs) and blood, through noninvasive liquid biopsies to monitor these systemic changes.<br /><br />The study highlighted the role of CD38, a NAD-consuming enzyme, as a potential biomarker to predict irAEs, specifically ICI-pneumonitis. The findings showed that a higher proportion of CD38-expressing immune cells, particularly in T cells within BALFs, correlated with an increased risk of developing ICI-pneumonitis compared to controls. At a single-cell level, CD38 was significantly upregulated in T cells of patients with ICI-pneumonitis, indicating a senescent-associated secretory phenotype.<br /><br />Furthermore, the study used external cohorts to validate these findings. It was found that CD38 expression in pre-ICI blood samples could predict a higher risk of irAEs, such as ICI-colitis, without correlating to a prolonged clinical response from ICI treatment. CD38 expression specifically increased in T cells from ICI-colitis samples, both before and after treatment.<br /><br />In conclusion, the research suggests that liquid biopsy detection of CD38 in bodily fluids could serve as an early indicator for patients at high risk of irAEs due to ICI treatments, helping in the management and mitigation of these therapy-related complications.

Asset Subtitle

Si-Cong Ma

Meta Tag

Speaker Si-Cong Ma

Topic Screening and Early Detection

Keywords

enzymomics

immune-related adverse events

immune checkpoint inhibition

liquid biopsies

CD38 biomarker

ICI-pneumonitis

T cells

ICI-colitis

senescent-associated secretory phenotype

autoimmune responses