WCLC 2025 - Posters & ePosters-P2.06.92 Host-Derived Biomarkers of Inflammation and Body Composition Predict Immunotherapy Outcomes in Advanced NSCLC

Pdf Summary

This study by Andrea De Giglio et al. investigates host-derived biomarkers of inflammation and body composition as predictors of immunotherapy outcomes in advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) improve survival but benefit only subsets of patients. Common biomarkers focus on tumor features (e.g., PD-L1), but host factors like systemic inflammation, metabolism, and muscle mass also influence responses.<br /><br />The prospective study enrolled 40 stage IIIB-IV NSCLC patients receiving first-line ICI or chemo-ICI. Plasma biomarkers measured at baseline and 90 days included sRAGE, FGF21, GDF15, and cPLIN2. Body composition (skeletal muscle index, fat areas) was assessed via CT. Inflammatory indices (LIPI, PLR, NLR, dNLR) and peripheral immune cell subsets were analyzed.<br /><br />Key findings:<br />- sRAGE (soluble receptor counteracting inflammation) correlated inversely with inflammation markers (LIPI, dNLR), stratified overall survival, and increased in responders, indicating prognostic and early dynamic biomarker potential.<br />- FGF21 and GDF15, markers of muscle catabolism and cachexia, were associated with sarcopenia, increased inflammation, immunosuppression, and predicted worse survival.<br />- cPLIN2, linked to lipid metabolism in adipose tissue, correlated with visceral fat and lower inflammatory indices, supporting a role in immune modulation.<br />- Sarcopenia was prevalent (72.5%) and linked to shorter progression-free and overall survival. Muscle loss over 3 months predicted higher mortality.<br /><br />The study highlights the importance of host-related factors—particularly inflammation markers and muscle mass—in shaping immunotherapy outcomes in advanced NSCLC. Integrating these biomarkers with tumor-based markers may improve patient stratification and personalized treatment approaches.<br /><br />In summary, sRAGE, FGF21, GDF15, and cPLIN2, combined with body composition data, offer insights into systemic inflammation and metabolic status impacting immunotherapy efficacy. Muscle mass loss remains a strong negative prognostic factor, emphasizing the need to consider host biology in cancer immunotherapy.

Asset Subtitle

Andrea De Giglio

Meta Tag

Speaker Andrea De Giglio

Topic Pathology and Biomarkers

Keywords

non-small cell lung cancer

immune checkpoint inhibitors

host-derived biomarkers

systemic inflammation

body composition

sRAGE

FGF21

GDF15

cPLIN2

sarcopenia