Previous studies have demonstrated that SPP1 plays a critical role in bone metabolism and homeostasis.[37] The expression level of SPP1 on macrophages had a noticeably strong correlation with tumor prognosis.[38] The macrophage‐specific knockout of SPP1 could significantly decrease the infiltration of cancer‐associated fibroblasts.[39] Here, we highlighted the functional roles of the SPP1/Integrin signaling pathway in cell–cell interactions between multiple immune cells and MgphiMSCs. This evidence concerns the gene SPP1 and cancer.