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One current approach is the combination of azacytidine (AZA) with checkpoint inhibitors; however, the potential benefit of targeting the immunomodulator indoleamine\u20102,3\u2010dioxygenase (IDO\u20101) has not yet been evaluated. We observed moderate to strong IDO\u20101 expression in 37% of patients with high\u2010risk MDS. IDO\u20101 positivity was predictive of treatment failure and shorter overall survival. Moreover, IDO\u20101 positivity correlated inversely with the number of infiltrating CD8<jats:sup>+<\/jats:sup> T cells, and IDO\u20101+ patients failed to show an increase in CD8<jats:sup>+<\/jats:sup> T cells under AZA treatment. <jats:italic>In vitro<\/jats:italic> experiments confirmed tryptophan catabolism and depletion of CD8<jats:sup>+<\/jats:sup> T cells in IDO\u20101+ MDS, suggesting that IDO\u20101 expression induces an immunosuppressive microenvironment in MDS, thereby leading to treatment failure under AZA treatment. In conclusion, IDO\u20101 is expressed in more than one\u2010third of patients with higher\u2010risk MDS, and is predictive of treatment failure and shorter overall survival. Therefore, IDO\u20101 is emerging as a promising predictor and therapeutic target, especially for combination therapies with HMAs or checkpoint inhibitors.<\/jats:p>","DOI":"10.1111\/bjh.16652","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T02:47:32Z","timestamp":1588214852000},"page":"361-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prognostic value of indoleamine 2,3 dioxygenase in patients with higher\u2010risk myelodysplastic syndromes treated with azacytidine"],"prefix":"10.1111","volume":"190","author":[{"given":"Catharina","family":"M\u00fcller\u2010Thomas","sequence":"first","affiliation":[{"name":"Department of Medicine I, Hematology and Oncology M\u00fcnchen Klinik Schwabing Munich Germany"},{"name":"Department of Medicine III, Hematology and Oncology Technische Universit\u00e4t M\u00fcnchen Munich 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