Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, United States.
Medical University of Vienna, Department of Medicine, Division of Bone Marrow Transplantation and Cellular Therapies, Vienna, Austria.
Curr Cancer Drug Targets. 2020;20(7):545-557. doi: 10.2174/1568009620666200421081455.
Despite recent therapeutic advancements, acute myeloid leukemia (AML) remains a challenging clinical entity with overall poor outcomes. Given the evident role of T cell-mediated immunity in response to allogeneic stem cell transplantation and donor lymphocyte infusions, strategies that enhance immune activation and mitigate immune dysfunction represent attractive therapeutic platforms to improve clinical outcomes in AML. Pre-clinical data suggest that immune dysfunction is a major contributor to AML progression and relapse. Increased expression of immune checkpoints such as programmed death 1 (PD-1) contributes to AML immune evasion and is associated with disease progression. Immune checkpoint inhibition is being explored in AML with early evidence of clinical activity, particularly in combination with cytotoxic chemotherapy and hypomethylating agents. In this review, we explore the scientific rationale behind the use of immune checkpoint inhibition either as single agents or in combination with hypomethylating agents or cytotoxic chemotherapy and provide a clinical update of both completed and ongoing trials in AML.
尽管最近有了治疗上的进展，但急性髓系白血病（AML）仍然是一种具有挑战性的临床实体，总体预后较差。鉴于 T 细胞介导的免疫在异基因干细胞移植和供者淋巴细胞输注中的明显作用，增强免疫激活和减轻免疫功能障碍的策略代表了改善 AML 临床结果的有吸引力的治疗平台。临床前数据表明，免疫功能障碍是 AML 进展和复发的主要原因。免疫检查点（如程序性死亡 1（PD-1））的表达增加有助于 AML 的免疫逃逸，并与疾病进展相关。免疫检查点抑制正在 AML 中进行探索，早期有临床活性的证据，特别是与细胞毒性化疗和低甲基化剂联合使用时。在这篇综述中，我们探讨了使用免疫检查点抑制作为单一药物或与低甲基化剂或细胞毒性化疗联合使用的科学依据，并提供了 AML 中已完成和正在进行的试验的临床更新。
