急性白血病的免疫疗法
Immune-Based Therapies in Acute Leukemia.
作者信息
Witkowski Matthew T, Lasry Audrey, Carroll William L, Aifantis Iannis
机构信息
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
出版信息
Trends Cancer. 2019 Oct;5(10):604-618. doi: 10.1016/j.trecan.2019.07.009. Epub 2019 Aug 29.
Treatment resistance remains a leading cause of acute leukemia-related deaths. Thus, there is an unmet need to develop novel approaches to improve outcome. New immune-based therapies with chimeric antigen receptor (CAR) T cells, bi-specific T cell engagers (BiTEs), and immune checkpoint blockers (ICBs) have emerged as effective treatment options for chemoresistant B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). However, many patients show resistance to these immune-based approaches. This review describes crucial lessons learned from immune-based approaches targeting high-risk B-ALL and AML, such as the leukemia-intrinsic (e.g., target antigen loss, tumor heterogeneity) and -extrinsic (e.g., immunosuppressive microenvironment) mechanisms that drive treatment resistance, and discusses alternative approaches to enhance the effectiveness of these immune-based treatment regimens.
治疗耐药性仍然是急性白血病相关死亡的主要原因。因此，开发新方法以改善治疗结果的需求尚未得到满足。嵌合抗原受体（CAR）T细胞、双特异性T细胞衔接器（BiTE）和免疫检查点阻断剂（ICB）等新型免疫疗法已成为化疗耐药性B细胞急性淋巴细胞白血病（B-ALL）和急性髓系白血病（AML）的有效治疗选择。然而，许多患者对这些基于免疫的方法表现出耐药性。本综述描述了从针对高危B-ALL和AML的基于免疫的方法中学到的关键经验教训，例如导致治疗耐药性的白血病内在（如靶抗原丢失、肿瘤异质性）和外在（如免疫抑制微环境）机制，并讨论了提高这些基于免疫的治疗方案有效性的替代方法。
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