Therefore, we investigated whether the modulation of PD-L1 expression in HNSCC cell lines with different PD-L1 intrinsic expression levels affects the capability of HNSCC cells’ spreading on surfaces coated with different extracellular matrix components (poly-L-lysine, collagen type 1, fibronectin and Matrigel® (laminin-rich matrix)). The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.