{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T11:17:02Z","timestamp":1772623022799,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Acute myeloid leukemia (AML), a malignant hematological stem cell disease, arises from the malignant transformation of myeloid progenitor cells. Among the genetic aberrations in AML, mutations in the tyrosine kinase receptor FLT3, especially FLT3-ITD, are most frequently detected and are correlated with poor clinical outcomes. Intriguingly, FLT3-ITD is implicated in immune escape, although the underlying mechanism remains elusive. The present study aims to elucidate the relationship between FLT3-ITD and the immune checkpoint molecule CD80, which is crucial for immune regulation. Our results provide compelling evidence that a moderate level of CD80 localizes on the cell surface of FLT3-ITD AML cells. Mechanistically, FLT3-ITD upregulates CD80 expression by increasing intracellular reactive oxygen species (ROS) levels and subsequent CD80 enhancement. Significantly, we found that treatment with a HIF-1\u03b1 inhibitor selectively suppressed the proliferation of FLT3-ITD-positive leukemic cells and induced excessive ROS production, which consequently led to CD80 overexpression. Collectively, our findings unravel the molecular pathway through which FLT3-ITD augments CD80 expression via ROS, suggesting a potential immune evasion. Moreover, this study points to a novel therapeutic strategy that combines chemotherapy-induced CD80 overexpression with immune checkpoint-targeted immunotherapy to eradicate FLT3-ITD AML cells.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1577313","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T04:10:36Z","timestamp":1752725436000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["FLT3-ITD promotes immune checkpoint CD80 via ROS elevation in acute myeloid 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