{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:49:25Z","timestamp":1790660965210,"version":"4.1.0"},"reference-count":22,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acute myeloid leukemia (AML) relapse is one of the most common and significant adverse events following allogeneic hematopoietic cell transplantation (HCT). Downregulation of major histocompatibility class II (MHC-II) surface expression on AML blasts may represent a mechanism of escape from the graft-versus-malignancy effect and facilitate relapse. We hypothesized that T-cell immunotherapies targeting AML antigens would upregulate MHC-II surface expression via localized release of interferon gamma (IFN-\u03b3), a protein known to upregulate MHC-II expression via JAK-STAT signaling. We demonstrate that flotetuzumab (FLZ), a CD123\u00a0\u00d7 CD3 bispecific DART molecule, and chimeric antigen receptor expressing T cells targeting CD123, CD33, or CD371 upregulate MHC-II surface expression in\u00a0vitro on a THP-1 AML cell line with intermediate MHC-II expression and 4 primary AML samples from patients relapsing after HCT with low MHC-II expression. We additionally show that FLZ upregulates MHC-II expression in a patient-derived xenograft model and in patients with relapsed or refractory AML who were treated with FLZ in a clinical trial. Finally, we report that FLZ-induced MHC-II upregulation is mediated by IFN-\u03b3. In conclusion, we provide evidence that T-cell immunotherapies targeting relapsed AML can kill AML via both MHC-independent mechanisms and by an MHC-dependent mechanism through local release of IFN-\u03b3 and subsequent upregulation of MHC-II expression.<\/jats:p>","DOI":"10.1182\/blood.2022017795","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T21:35:55Z","timestamp":1671831355000},"page":"1718-1723","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":30,"title":["Flotetuzumab and other T-cell immunotherapies upregulate MHC class II expression on acute myeloid leukemia cells"],"prefix":"10.1182","volume":"141","author":[{"given":"Joseph C.","family":"Rimando","sequence":"first","affiliation":[{"name":"1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, 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