TY - JOUR AU - Chiang, Chi-Shiun AU - Fu, Sheng-Yung AU - Wang, Shu-Chi AU - Yu, Ching-Fang AU - Chen, Fang-Hsin AU - Lin, Chi-Min AU - Hong, Ji-Hong PY - 2012 M3 - Original Research TI - Irradiation Promotes an M2 Macrophage Phenotype in Tumor Hypoxia JO - Frontiers in Oncology UR - https://www.frontiersin.org/articles/10.3389/fonc.2012.00089 VL - 2 SN - 2234-943X N2 - Macrophages display different phenotypes with distinct functions and can rapidly respond to environmental changes. Previous studies on TRAMP-C1 tumor model have shown that irradiation has a strong impact on tumor microenvironments. The major changes include the decrease of microvascular density, the increase of avascular hypoxia, and the aggregation of tumor-associated macrophages in avascular hypoxic regions. Similar changes were observed no matter the irradiation was given to tissue bed before tumor implantation (pre-IR tumors), or to established tumors (IR tumors). Recent results on three murine tumors, TRAMP-C1 prostate adenocarcinoma, ALTS1C1 astrocytoma, and GL261 glioma, further demonstrate that different phenotypes of inflammatory cells are spatially distributed into different microenvironments in both IR and pre-IR tumors. Regions with avascular hypoxia and central necrosis have CD11bhigh/Gr-1+ neutrophils in the center of the necrotic area. Next to them are CD11blow/F4/80+ macrophages that sit at the junctions between central necrotic and surrounding hypoxic regions. The majority of cells in the hypoxic regions are CD11blow/CD68+ macrophages. These inflammatory cell populations express different levels of Arg I. This distribution pattern, except for neutrophils, is not observed in tumors receiving chemotherapy or an anti-angiogenesis agent which also lead to avascular hypoxia. This unique distribution pattern of inflammatory cells in IR tumor sites is interfered with by targeting the expression of a chemokine protein, SDF-1α, by tumor cells, and this also increases radiation-induced tumor growth delay. This indicates that irradiated-hypoxia tissues have distinct tumor microenvironments that favor the development of M2 macrophages and that is affected by the levels of tumor-secreted SDF-1α. ER -