{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:54:53Z","timestamp":1790762093090,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor cells respond to IFN-\u03b3 of activated T cells to upregulate programmed death-ligand 1 (PD-L1) in the tumor microenvironment as an adaptive immune resistance mechanism. Tumor cells also express oncogene-driven PD-L1. PD-L1 is also expressed on myeloid-derived suppressor cells (MDSCs). It is known that both type I and II IFNs upregulate PD-L1 expression in MDSCs. However, the molecular mechanism underlying PD-L1 expression in MDSCs is still largely unknown. We report in this article that MDSCs exhibit constitutive STAT1 phosphorylation in vitro without exogenous IFNs, indicating a constitutive active JAK-STAT signaling pathway in mouse MDSCs in vitro. Furthermore, IFN-\u03b1 and IFN-\u03b2 but not IFN-\u03b3 are endogenously expressed in the MDSC cell line in vitro and in tumor-induced MDSCs in vivo. Neutralizing type I IFN or inhibiting the JAK-STAT signaling pathway significantly decreased constitutive PD-L1 expression in MDSCs in vitro. However, neither IFN-\u03b1 expression level nor IFN-\u03b2 expression level is correlated with PD-L1 expression level in MDSCs; instead, the level of IFN receptor type I (IFNAR1) is correlated with PD-L1 expression levels in MDSCs. Consequently, knocking out IFNAR1 in mice diminished PD-L1 expression in tumor-induced MDSCs. Therefore, we determined that 1) PD-L1 expression in MDSCs is activated by type I IFN through an autocrine manner and 2) the expression level of PD-L1 is controlled at least in part by the IFNAR1 level on MDSCs. Our data indicate that MDSCs may maintain their PD-L1 expression via autocrine type I IFN to exert their suppressive activity in the absence of IFN-\u03b3 from the suppressed T cells in the tumor microenvironment.<\/jats:p>","DOI":"10.4049\/jimmunol.1800129","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T10:25:25Z","timestamp":1526034325000},"page":"264-277","source":"Crossref","is-referenced-by-count":92,"title":["IFNAR1 Controls Autocrine Type I IFN Regulation of PD-L1 Expression in Myeloid-Derived Suppressor Cells"],"prefix":"10.1093","volume":"201","author":[{"given":"Wei","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Klement","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia , Augusta, GA 30912"},{"name":"Georgia Cancer Center, Medical College of Georgia , Augusta, GA 30912"},{"name":"Charlie Norwood Veterans Affairs Medical Center , Augusta, GA 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia , Augusta, GA 30912"},{"name":"Georgia Cancer Center, Medical College of Georgia , Augusta, GA 30912"},{"name":"Charlie Norwood Veterans Affairs Medical Center , Augusta, GA 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2482-6811","authenticated-orcid":false,"given":"Mohammed L","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia , Augusta, GA 30912"},{"name":"Georgia Cancer Center, Medical College of Georgia , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kebin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia , Augusta, GA 30912"},{"name":"Georgia Cancer Center, Medical College of Georgia , Augusta, GA 30912"},{"name":"Charlie Norwood Veterans Affairs Medical Center , Augusta, GA 30904"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,1]]},"reference":[{"key":"2025030417565897800_r1","doi-asserted-by":"crossref","first-page":"12150","DOI":"10.1038\/ncomms12150","article-title":"Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards","volume":"7","author":"Bronte","year":"2016","journal-title":"Nat. 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