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

2024-02-29Journal article Open access
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dc.contributor.authorMa, Jingyi
dc.contributor.authorMoussawi, Khatoun Al
dc.contributor.authorLou, Hantao
dc.contributor.authorChan, Hok Fung
dc.contributor.authorWang, Yihua
dc.contributor.authorChadwick, Joseph
dc.contributor.authorPhetsouphanh, Chansavath
dc.contributor.authorSlee, Elizabeth A.
dc.contributor.authorZhong, Shan
dc.contributor.authorLeissing, Thomas M.
dc.contributor.authorRoth, Andrew
dc.contributor.authorQin, Xiao
dc.contributor.authorChen, Shuo
dc.contributor.authorYin, Jie
dc.contributor.authorRatnayaka, Indrika
dc.contributor.authorHu, Yang
dc.contributor.authorLouphrasitthiphol, Pakavarin
dc.contributor.authorTaylor, Lewis
dc.contributor.authorBettencourt, Paulo J. G.
dc.contributor.authorMuers, Mary
dc.contributor.authorGreaves, David R.
dc.contributor.authorMcShane, Helen
dc.contributor.authorGoldin, Robert
dc.contributor.authorSoilleux, Elizabeth J.
dc.contributor.authorColeman, Mathew L.
dc.contributor.authorRatcliffe, Peter J.
dc.contributor.authorLu, Xin
dc.date.accessioned2024-03-06T12:16:13Z
dc.date.available2024-03-06T12:16:13Z
dc.date.issued2024-02-29
dc.description.abstractHypoxia 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1073/pnas.2309957121pt_PT
dc.identifier.eid85186308201
dc.identifier.issn0027-8424
dc.identifier.pmid38422022
dc.identifier.urihttp://hdl.handle.net/10400.14/44141
dc.identifier.wos001207786500003
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectTumor microenvironmentpt_PT
dc.subjectHypoxia-inducible factorpt_PT
dc.subjectFactor-inhibiting HIFpt_PT
dc.subjectB cell lymphomapt_PT
dc.subjectTumor suppressionpt_PT
dc.titleDeficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue10pt_PT
oaire.citation.titleProceedings of the National Academy of Sciences of the United States of Americapt_PT
oaire.citation.volume121pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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