REVIEW article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1605669
This article is part of the Research TopicLocalized Immunomodulation Approaches for Transplantation ToleranceView all 4 articles
Targeting Hypoxia-Inducible Factor 1α in Chronic Graft-Versus-Host Disease to Enhance Graft-Versus-Leukemia Responses: Implications for Nanotherapeutics
Provisionally accepted
- 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 2960th Hospital of the PLA, Jinan, Shandong Province, China
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Chronic graft-versus-host disease (cGVHD), a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), arises from donor immune cell-mediated tissue damage, chronic inflammation, and fibrosis. Current therapies fail to adequately address fibrotic progression and heighten infection risks, underscoring the need for targeted strategies. Hypoxia-inducible factor-1α (HIF-1α), a pivotal regulator, emerges as a potential therapeutic target by orchestrating immunometabolic homeostasis, suppressing fibrosis, preserving gut microbiota balance, and retaining graft-versus-leukemia (GVL) effects. However, clinical translation necessitates overcoming challenges in tissue specificity and off-target effects. Smart nanodelivery systems hold promise for enhancing precision to enable localized HIF-1α pathway modulation. This review highlights the multidimensional roles of HIF-1α in cGVHD pathogenesis and proposes nanotherapeutic approaches to reconcile immunofibrotic imbalances, advancing a paradigm shift in cGVHD management while preserving GVL efficacy.
Keywords: HIF-1α, Chronic graft-versus-host disease, Immunomodulation, Fibrosis, graft-versus-leukemia, Nanomedicine
Received: 03 Apr 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Wang and Zhou. 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: Fang Zhou, 960th Hospital of the PLA, Jinan, Shandong Province, China
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