BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1577313
This article is part of the Research TopicPrecision Immunotherapy and Novel Target Discovery in Hematological MalignancyView all 14 articles
FLT3-ITD promotes immune checkpoint CD80 via ROS elevation in acute myeloid leukemia
Provisionally accepted
- 1Beijing Friendship Hospital, Capital Medical University, Beijing, China
- 2Department of Scientific Research, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- 3School of Stomatology and Ophthalmology, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
- 4Department of Oncology, Wuming Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
- 5Department of Clinical Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China
- 6Department of Clinical Medicine, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China
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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-1α 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 3 immune checkpoint-targeted immunotherapy to eradicate FLT3-ITD AML cells.
Keywords: Immune checkpoint, CD80, ROS, FLT3-ITD, Leukemia
Received: 15 Feb 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Yang, Yan, Zhang, Wang, Xu and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mengzhe Yang, Beijing Friendship Hospital, Capital Medical University, Beijing, China
Tao Ren, Department of Clinical Medicine, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China
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