In established tumors, cancer cells reeducate TAMs to an immunosuppressive anti-inflammatory phenotype that supports tumor growth and facilitates tumor progression via the production of diverse tumor growth factors (e.g., EGF, FGF, TGFb, and PDGF), proangiogenic molecules (e.g., VEGF-A, SPP1, YKL-40, TIE2, and CXCL8), immunosuppressive factors (e.g., IL-10, PD-L1, CCL17, PGE, CCL20, and ROS), and matrix remodeling factors (e.g., matrix metalloproteinases [MMPs], uPAs, SPARC, and cathepsins) [17, 144, 145]. Here, SPP1 is linked to neoplasm.