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Understanding the immune regulatory mechanisms employed by acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells upon exposure to IFN-\u03b3 is critical for development of immunotherapy and checkpoint blockade therapy approaches. This study aims to explore the influence of myeloid maturation on IFN-\u03b3-induced PD-L1 and PD-L2 expression and on pro-leukemogenic transcription factor STAT3 signaling in AML and MDS. Stimulation of myeloid blasts\u2019 maturation by all-trans retinoic acid (ATRA) or 1\u03b1,25-dihydroxyvitamin D3 (vitamin D) increased the CD11b<jats:sup>+<\/jats:sup> fraction that expressed PD-1 ligands in response to IFN-\u03b3. Intriguingly, STAT3 pathway was potently induced by IFN-\u03b3 and strengthened upon prolonged exposure. Nonetheless, STAT3-mediated atypical IFN-\u03b3 signaling appeared as a negligible factor for PD-L1 and PD-L2 expression. These negative influences of IFN-\u03b3 could be alleviated by a small-molecule inhibitor of STAT3, stattic, which also inhibited\u00a0the upregulation of PD-L1. In conclusion, induction of myeloid maturation enhances the responsiveness of AML and MDS cells to IFN-\u03b3. However, these malignant myeloid cells can exploit both STAT3 pathway and PD-1 ligands to survive IFN-\u03b3-mediated immunity and maintain secondary immune resistance.<\/jats:p>","DOI":"10.1038\/s41598-019-48256-4","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T10:03:15Z","timestamp":1565604195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Myeloid maturation potentiates STAT3-mediated atypical IFN-\u03b3 signaling and upregulation of PD-1 ligands in AML and MDS"],"prefix":"10.1038","volume":"9","author":[{"given":"Digdem","family":"Yoyen-Ermis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurcan","family":"Tunali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ece","family":"Tavukcuoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utku","family":"Horzum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Ozkazanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"Sutlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"Buyukasik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes","family":"Esendagli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"48256_CR1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.it.2017.04.004","volume":"38","author":"EK Curran","year":"2017","unstructured":"Curran, E. 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