FIGURE 6.

Lipid accumulation polarizes macrophages to an M2‐like state that is critical for pro–tumor potential via PI3K‐γ. A, The top enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set in tumor‐associated macrophages (TAM) from the MFC‐bearing tumor model is shown. B, WB immunoblotting of indicated proteins in M0 and M2 macrophages. C, Immunoblotting in macrophages treated with 30% MFC‐tumor explant supernatant (TES) and 2 µg/mL exo‐lipid mixtures for 48 h. D, E, Representative overlay histogram (D) and quantification (E) showing PI3K‐γ inhibitor (IPI549) reverse the high expression of CD206 in MFC‐TES‐treated macrophages. n = 5; three experimental repeats. Data are mean + SEM; ***P < 0.001. F, Representative histograms showing the phagocytosis by macrophage treated with 30% MFC‐TES and/or IPI549. G, Analysis of phagocytosis in macrophage treated with 30% MFC‐TES and/or IPI549. n = 5. ***P < 0.001. H, Mean tumor volume of MFC murine gastric cancer in 615 mice administered with IPI‐549 versus vehicle‐treatment (n = 8). Data are mean ± SEM; ****P < 0.0001. I, Individual tumor volumes of intradermal MFC implants in mice treated with IPI‐549 or vehicle (n = 8)