Identification of prognostic liquid biopsy biomarkers in patients with cutaneous squamous cell carcinoma treated with cemiplimab

Background: The treatment of Cutaneous Squamous Cell Carcinoma (CSCC) has undergone significant changes with the introduction of Immune Checkpoint Inhibitors (ICIs). While promising results have been observed, their efficacy remains limited to a subset of patients. Soluble immune checkpoint molecules, Interferon-gamma (IFN-γ), and cell-free DNA (cfDNA) could serve as potential biomarkers, particularly in ICI-based therapies. Methods: In this study, we assessed the prognostic role of serum PD-L1, LAG-3, TIM-3, CTLA-4, IFN-γ, and plasma cfDNA in a cohort of 41 advanced (locally-advanced or metastatic) CSCC patients treated with the anti-PD-1 inhibitor cemiplimab. Results: Our findings indicate that elevated baseline serum levels of IFN-γ are significantly associated with poorer treatment response and shorter Progression-Free Survival (PFS) in patients receiving cemiplimab. Moreover, patients with worse outcomes in terms of response and PFS exhibited a post-treatment decrease in IFN-γ levels. Higher baseline levels of plasma cfDNA and serum CTLA-4 demonstrated a trend toward association with unfavourable clinical outcomes. Conclusions: These results highlight the potential of baseline and post-treatment IFN-γ levels as significant prognostic indicators for advanced CSCC patients undergoing cemiplimab therapy.