HIF-1α inhibitor echinomycin reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect

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• 作者：Yushi Yao ; Lei Wang ; Jihao Zhou ; Xinyou Zhang
• 关键词：Acute graft ; versus ; host disease ; Graft ; versus ; leukemia effect ; Hypoxia ; inducible factor 1 alpha ; Echinomycin ; Regulatory T cells ; Th17 cells
• 刊名：Journal of Translational Medicine
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：15
• 期：1
• 全文大小：1603KB
• 刊物主题：Biomedicine, general; Medicine/Public Health, general;
• 出版者：BioMed Central
• ISSN：1479-5876
• 卷排序：15

文摘

BackgroundAcute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding. Hypoxia-inducible factor 1 alpha (HIF-1α) is a key molecule switch that attenuates Treg but promotes Th17 development. However, whether pharmacological inhibition of HIF-1α reduces aGVHD via increasing Treg development and diminishing Th17 responses remains unexplored.