SPP1 and head and neck squamous cell carcinoma: To investigate the direct or indirect effects of SPP1 + Macs on HNSCC cells, cell culture supernatants from the SPP1-negative control (SPP1-NC; SPP1-NC THP-1 cell-derived macrophages) group and the SPP1-overexpressing (SPP1-OE; SPP1-OE THP-1 cell-derived macrophages) group were collected for further indirect culture with HN6 and CAL27 cells, while another coculture model was used to explore the direct effects (Fig. 3C).