Single-cell studies have shown that SPP1+ macrophages play a crucial role in the TME, and are associated with poor prognosis in CRC patients.17, 18, 19, 20SPP1 (secreted phosphoprotein 1), also known as osteopontin, is overexpressed in various cancer types21, 22, 23 and is implicated in promoting CRC progression and metastasis through EMT and hypoxia pathways.24 Here, SPP1 is linked to colorectal carcinoma.