火炬的两端：STAT3缺乏如何阻断移植物抗宿主疾病同时保持移植物抗白血病活性。
Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity.
发表日期：2023 Aug 01
作者：
Joshua D Brandstadter, Riley Outen, Ivan Maillard
来源：
Cell Death & Disease
摘要：
同种异基因造血细胞移植（ahct）可以通过移植物来源的免疫细胞清除移植物反对白血病（GVL）效应，从而治愈高危白血病患者。然而，通过调控与移植物抗宿主病（GVHD）相关的炎症和宿主器官损伤这一问题一直是同种异基因造血移植面临的最大障碍。这种强大的、治愈目标的疗法仍然是血液科医生药箱中最有毒的治疗方法之一，因为GVHD相关的发病率、感染和白血病复发风险相结合。在本期《JCI》上，Li, Wang等人报告说通过PD-L1/PD-1依赖性的组织特异性程序性死亡配体1/程序性细胞死亡蛋白1依赖性（PD-L1/PD-1依赖性）生物能改变可以从GVHD中解救出GVL效应，从而在GVHD的靶器官中减弱有害的T细胞效应，同时保留它们在淋巴造血组织中的有益的抗肿瘤活性。
Allogeneic hematopoietic cell transplantation can cure patients with high-risk leukemia through graft-versus-leukemia (GVL) effects, the process by which malignant leukemic cells are cleared by donor-derived immune cells from the graft. The problem of harnessing GVL effects while controlling inflammation and host-organ damage linked with graft-versus-host disease (GVHD) has been the most formidable hurdle facing allogeneic hematopoietic cell transplantation. This powerful, curative-intent therapy remains among the most toxic treatments in the hematologist's armamentarium due to the combined risks of GVHD-related morbidity, infections, and leukemia relapse. In this issue of the JCI, Li, Wang, et al. report that T cell Stat3 deficiency can extricate GVL effects from GVHD through tissue-specific programmed death-ligand 1/programmed cell death protein 1-dependent (PD-L1/PD-1-dependent) bioenergetic alterations that blunt harmful T cell effects in GVHD target organs, while preserving their beneficial antitumor activity in lymphohematopoietic tissues.