Teshima Takanori, Hill Geoffrey R
Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Front Immunol. 2021 Aug 19;12:715424. doi: 10.3389/fimmu.2021.715424. eCollection 2021.
Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for hematologic malignancies, bone marrow failure syndromes, and inherited immunodeficiencies and metabolic diseases. Graft--host disease (GVHD) is the major life-threatening complication after allogeneic HCT. New insights into the pathophysiology of GVHD garnered from our understanding of the immunological pathways within animal models have been pivotal in driving new therapeutic paradigms in the clinic. Successful clinical translations include histocompatibility matching, GVHD prophylaxis using cyclosporine and methotrexate, posttransplant cyclophosphamide, and the use of broad kinase inhibitors that inhibit cytokine signaling (e.g. ruxolitinib). New approaches focus on naïve T cell depletion, targeted cytokine modulation and the inhibition of co-stimulation. This review highlights the use of animal transplantation models to guide new therapeutic principles.
异基因造血细胞移植（HCT）是治疗血液系统恶性肿瘤、骨髓衰竭综合征以及遗传性免疫缺陷和代谢性疾病的一种治愈性疗法。移植物抗宿主病（GVHD）是异基因HCT后主要的危及生命的并发症。基于我们对动物模型免疫途径的理解，在GVHD病理生理学方面获得的新见解对推动临床新的治疗模式起到了关键作用。成功的临床转化包括组织相容性匹配、使用环孢素和甲氨蝶呤预防GVHD、移植后环磷酰胺以及使用抑制细胞因子信号传导的广谱激酶抑制剂（如鲁索替尼）。新方法聚焦于清除初始T细胞、靶向细胞因子调节以及共刺激抑制。本综述重点介绍了利用动物移植模型来指导新的治疗原则。
