Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, USA.
Leuk Lymphoma. 2019 Dec;60(14):3350-3362. doi: 10.1080/10428194.2019.1639167. Epub 2019 Jul 23.
Immunotherapy in the form of allogeneic stem cell transplantation (SCT) plays an instrumental role in the treatment of acute myeloid leukemia (AML), with non-transplant modalities of immunotherapy including checkpoint blockade now being actively explored. Here, we provide an overview of the graft versus leukemia (GVL) effect in AML as a window into understanding the prospects of AML immunotherapy. We explore the roles of various cell types in orchestrating anti-leukemic immunity, as well as those contributing to the unique immune suppressive state of myeloid diseases. We discuss specific approaches to engage the immune system, while noting the challenges of the AML antigen landscape and the barriers to immune modulation. We review the potential for immunomodulatory agents in combination with cellular therapies, donor lymphocyte infusion, and following SCT. Finally, to address the challenge of minimal residual disease (MRD) following chemotherapy, we propose combination epigenetic and immunotherapy for the eradication of MRD.
同种异体干细胞移植（SCT）形式的免疫疗法在急性髓系白血病（AML）的治疗中起着重要作用，非移植免疫疗法包括检查点阻断，目前正在积极探索。在这里，我们提供了 AML 中移植物抗白血病（GVL）效应的概述，以了解 AML 免疫疗法的前景。我们探讨了各种细胞类型在调节抗白血病免疫中的作用，以及在髓系疾病中独特的免疫抑制状态中发挥作用的细胞类型。我们讨论了特定的方法来激活免疫系统，同时注意 AML 抗原景观的挑战和免疫调节的障碍。我们综述了免疫调节剂与细胞疗法、供者淋巴细胞输注以及 SCT 后联合应用的潜力。最后，为了解决化疗后微小残留病（MRD）的问题，我们提出了联合表观遗传学和免疫疗法来消除 MRD。
