To investigate whether TAM-SPP1+ could promote cancer cell survival via mediating TIME, Hepa1-6 and Spp1-KO bone marrow-derived macrophage (BMDM) from Spp1–/– mice32,33 or control BMDM from C57BL/6J mice were mixed and implanted subcutaneously to establish a tumor-bearing model (Fig. 6b, details in Materials and Methods). This evidence concerns the gene SPP1 and cancer.