Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway

dc.contributor.authorAlicea-Torres, Kevin
dc.contributor.authorSanseviero, Emilio
dc.contributor.authorGui, Jun
dc.contributor.authorChen, Jinyun
dc.contributor.authorVeglia, Filippo
dc.contributor.authorYu, Qiujin
dc.contributor.authorDonthireddy, Laxminarasimha
dc.contributor.authorKossenkov, Andrew
dc.contributor.authorLin, Cindy
dc.contributor.authorFu, Shuyu
dc.contributor.authorMulligan, Charles
dc.contributor.authorNam, Brian
dc.contributor.authorMasters, Gregory
dc.contributor.authorDenstman, Fred
dc.contributor.authorBennett, Joseph
dc.contributor.authorHockstein, Neil
dc.contributor.authorRynda-Apple, Agnieszka
dc.contributor.authorNefedova, Yulia
dc.contributor.authorFuchs, Serge Y.
dc.contributor.authorGabrilovich, Dmitry I.
dc.date.accessioned2022-08-04T21:56:32Z
dc.date.available2022-08-04T21:56:32Z
dc.date.issued2021-03
dc.description.abstractMyeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism that restricts acquisition of suppressive activity by these cells. Downregulation of the IFNAR1 chain of this receptor is found in MDSC from cancer patients and mouse tumor models. The decrease in IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype. Whereas deletion of IFNAR1 is not sufficient to convert neutrophils and monocytes to MDSC, genetic stabilization of IFNAR1 in tumor bearing mice undermines suppressive activity of MDSC and has potent antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect. Thus, negative regulatory mechanisms of MDSC function can be exploited therapeutically.en_US
dc.identifier.citationAlicea-Torres, K., Sanseviero, E., Gui, J., Chen, J., Veglia, F., Yu, Q., ... & Gabrilovich, D. I. (2021). Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway. Nature communications, 12(1), 1-13.en_US
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/16996
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.rightsCC BYen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleImmune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathwayen_US
dc.typeArticleen_US
mus.citation.extentfirstpage1en_US
mus.citation.extentlastpage13en_US
mus.citation.issue1en_US
mus.citation.journaltitleNature Communicationsen_US
mus.citation.volume12en_US
mus.data.thumbpage6en_US
mus.identifier.doi10.1038/s41467-021-22033-2en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.departmentMicrobiology & Cell Biology.en_US
mus.relation.universityMontana State University - Bozemanen_US

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