On the other hand, the function of Spp1+ TAM may rely on the high Spp1 expression, which has not only been suggested as a negative prognostic factor for multiple cancer types,66 but also considered a potential drug target for cancer treatment.67,68 Indeed, the role of SPP1 has been mostly demonstrated in TAMs, and significant enrichment of SPP1+ TAMs within the TME is implicated in promoting tumor progression.32,54,62 Importantly, We observed the greatest reduction of Spp1-related interaction strength between macrophage and tumor cells in the PW group. Here, SPP1 is linked to neoplasm.