| First Author | Nishide S | Year | 2019 |
| Journal | iScience | Volume | 19 |
| Pages | 940-954 | PubMed ID | 31518902 |
| Mgi Jnum | J:347367 | Mgi Id | MGI:6717596 |
| Doi | 10.1016/j.isci.2019.08.033 | Citation | Nishide S, et al. (2019) Controlling the Phenotype of Tumor-Infiltrating Macrophages via the PHD-HIF Axis Inhibits Tumor Growth in a Mouse Model. iScience 19:940-954 |
| abstractText | The tumor microenvironment (TME) polarizes tumor-infiltrating macrophages toward tumor support. Macrophage-abundant tumors are highly malignant and are the cause of poor prognosis and therapeutic resistance. In this study, we show that the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) inhibits tumor growth of macrophage-abundant tumors and prolongs mouse survival. FG not only normalizes tumor vessels and improves tumor oxygenation but also directly affects macrophages and activates phagocytosis through the PHD-hypoxia-inducible factor (HIF) axis. Remarkably, FG can promote phagocytic ability of the Ly6C(lo) subset of tumor-infiltrating macrophages, leading to tumor growth inhibition. Moreover, Ly6C(neg) macrophages contributed to blood vessel normalization. Using a malignant tumor mouse model, we characterized macrophage function and subsets. Altogether, our findings suggest that the PHD inhibitor can promote the anti-tumor potential of macrophages to improve cancer therapy. |
