| First Author | Ma J | Year | 2024 |
| Journal | Proc Natl Acad Sci U S A | Volume | 121 |
| Issue | 10 | Pages | e2309957121 |
| PubMed ID | 38422022 | Mgi Jnum | J:346095 |
| Mgi Id | MGI:7614224 | Doi | 10.1073/pnas.2309957121 |
| Citation | Ma J, et al. (2024) Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment. Proc Natl Acad Sci U S A 121(10):e2309957121 |
| abstractText | Hypoxia 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. |
