Impact and dynamics of monocyte and platelet activation on clinical outcomes in patients under immune checkpoint inhibitors.

Introduction Immune checkpoint inhibitors (ICIs) are essential components of modern cancer therapy, yet biomarkers predicting treatment response and immune-related adverse events (irAEs) remain undefined. Thromboembolic complications are increasingly recognized during ICI therapy and are associated with elevated morbidity and mortality. However, the contribution of ICIs to venous and arterial thromboembolic events (VTE/ATE) remains unclear. This study longitudinally evaluates monocyte and platelet activation markers in patients receiving ICIs to determine whether these thromboinflammatory effector cells acquire a procoagulant phenotype during treatment and how this phenotype influences therapeutic outcomes. Method This prospective single-center cohort study at the University Medical Center Hamburg-Eppendorf analyses patients with lung cancer, head and neck cancer, or malignant melanoma receiving ICIs. Platelet (PAC-1, P-selectin, CD63) and monocyte (CD40, tissue factor, PD-1, PD-L1) activation markers are assessed by flow cytometry at baseline and at 1, 3, and 6 months. Longitudinal changes are analyzed using linear mixed-effects models, and baseline markers are correlated with clinical outcomes via Cox regression, log-rank tests, and ROC analysis. Results To date, 113 patients have been enrolled since September 2023, including 70 with melanoma, 30 with lung cancer, and 8 with HNSCC ([ Table 1 ]). In melanoma patients, monocyte PD-L1 expression was significantly elevated at month 6 compared with baseline (p