Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment

Jingyi Ma, Khatoun Al Moussawi, Hantao Lou, Hok Fung Chan, Yihua Wang, Joseph Chadwick, Chansavath Phetsouphanh, Elizabeth A. Slee, Shan Zhong, Thomas M. Leissing, Andrew Roth, Xiao Qin, Shuo Chen, Jie Yin, Indrika Ratnayaka, Yang Hu, Pakavarin Louphrasitthiphol, Lewis Taylor, Paulo J. G. Bettencourt, Mary MuersDavid R. Greaves, Helen McShane, Robert Goldin, Elizabeth J. Soilleux, Mathew L. Coleman, Peter J. Ratcliffe, Xin Lu

Resultado de pesquisarevisão de pares

2 Citações (Scopus)
13 Transferências (Pure)

Resumo

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.
Idioma originalEnglish
Número do artigoe2309957121
Número de páginas12
RevistaProceedings of the National Academy of Sciences of the United States of America
Volume121
Número de emissão10
DOIs
Estado da publicaçãoPublicado - 29 fev. 2024

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