Browsing by Author "Chadwick, Joseph"
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- Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironmentPublication . Ma, Jingyi; Moussawi, Khatoun Al; Lou, Hantao; Chan, Hok Fung; Wang, Yihua; Chadwick, Joseph; Phetsouphanh, Chansavath; Slee, Elizabeth A.; Zhong, Shan; Leissing, Thomas M.; Roth, Andrew; Qin, Xiao; Chen, Shuo; Yin, Jie; Ratnayaka, Indrika; Hu, Yang; Louphrasitthiphol, Pakavarin; Taylor, Lewis; Bettencourt, Paulo J. G.; Muers, Mary; Greaves, David R.; McShane, Helen; Goldin, Robert; Soilleux, Elizabeth J.; Coleman, Mathew L.; Ratcliffe, Peter J.; Lu, XinHypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.