Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, United States.
Department of Hematology/Hematopoietic Cell Transplantation, Beckman Research Institute at City of Hope National Medical Center, Duarte, CA, United States.
Front Immunol. 2018 Dec 21;9:3061. doi: 10.3389/fimmu.2018.03061. eCollection 2018.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies (i.e. leukemia and lymphoma), because graft-versus-leukemia (GVL) activity mediated by alloreactive T cells can eliminate residual malignant cells and prevent relapse. However, the same alloreactive T cells also mediate a severe side effect, graft-versus-host disease (GVHD), and prevention of GVHD while preserving GVL activity remains an elusive goal. The immune checkpoint molecule PD-L1 and its interaction with PD-1 receptor in regulating cancer immunity is under intensive and wide-spread study, but knowledge about this interaction in regulating GVHD and GVL activity is very limited. In this review, we summarize the literature exploring how PD-L1 interaction with its receptors PD-1 and CD80 regulate GVHD and GVL activities, how PD-L1 signaling regulates T cell metabolic profiles, and how a differential role of PD-L1 interaction with PD-1, CD80 or both may provide a novel avenue to prevent GVHD while preserving strong GVL effects.
同种异体造血细胞移植（HCT）是治疗血液系统恶性肿瘤（如白血病和淋巴瘤）的一种有治愈可能的疗法，因为同种异体反应性 T 细胞介导的移植物抗白血病（GVL）活性可以消除残留的恶性细胞并防止复发。然而，相同的同种异体反应性 T 细胞也介导了一种严重的副作用，移植物抗宿主病（GVHD），而在保留 GVL 活性的同时预防 GVHD 仍然是一个难以实现的目标。免疫检查点分子 PD-L1 及其与 PD-1 受体的相互作用在调节癌症免疫方面受到广泛而深入的研究，但关于这种相互作用在调节 GVHD 和 GVL 活性方面的知识非常有限。在这篇综述中，我们总结了探索 PD-L1 与其受体 PD-1 和 CD80 相互作用如何调节 GVHD 和 GVL 活性、PD-L1 信号如何调节 T 细胞代谢谱以及 PD-L1 与 PD-1、CD80 或两者的相互作用的不同作用如何为预防 GVHD 同时保留强大的 GVL 效应提供新的途径。
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