Wagner Tim¹, Krüger Finn², Franke Julia³, Krüger David⁴, Hoffmann Sarah⁵, Lange Paul⁶, Wagner Ben⁷
ABSTRACT:
Soluble immune checkpoint molecules (sICMs), including soluble PD-L1 (sPD-L1), CTLA-4 (sCTLA-4), and LAG-3 (sLAG-3), have emerged as dynamic biomarkers reflecting tumor immune evasion and response to immunotherapy. This review evaluates their role in quantifying tumor burden and predicting therapeutic outcomes across malignancies. Elevated baseline sPD-L1 (>3.5 ng/mL) correlates with advanced tumor stage (OR 4.2), while decreasing sCTLA-4 during anti-PD-1 therapy predicts prolonged progression-free survival (HR 0.45). We discuss detection technologies (ELISA, Luminex®), mechanistic insights into sICM-mediated immunosuppression, and clinical applications for monitoring immune-related adverse events (irAEs). Challenges in assay standardization and biological variability are addressed, with future directions emphasizing multi-analyte panels and AI-driven integration of sICMs with radiomic/clinical data for precision immuno-oncology.