Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan.
Int J Mol Sci. 2023 Feb 13;24(4):3727. doi: 10.3390/ijms24043727.
Hypomethylating agents (HMAs) have been used for decades in the treatment of hematologic neoplasms, and now, have gathered attention again in terms of their combination with potent molecular-targeted agents such as a BCL-6 inhibitor venetoclax and an inhibitor ivosidenib, as well as a novel immune-checkpoint inhibitor (anit-CD47 antibody) megrolimab. Several studies have shown that leukemic cells have a distinct immunological microenvironment, which is at least partially due to genetic alterations such as the mutation and epigenetic dysregulation. HMAs possibly improve intrinsic anti-leukemic immunity and sensitivity to immune therapies such as PD-1/PD-L1 inhibitors and anti-CD47 agents. This review describes the immuno-oncological backgrounds of the leukemic microenvironment and the therapeutic mechanisms of HMAs, as well as current clinical trials of HMAs and/or venetoclax-based combination therapies.
去甲基化药物（HMAs）已在血液系统恶性肿瘤的治疗中使用了数十年，现在，由于它们与强效的分子靶向药物（如 BCL-6 抑制剂 venetoclax 和 IDH1 抑制剂ivosidenib，以及新型免疫检查点抑制剂（抗-CD47 抗体）megrolimab）联合使用，再次受到关注。多项研究表明，白血病细胞具有独特的免疫微环境，这至少部分归因于基因突变和表观遗传失调等遗传改变。HMAs 可能会改善内在的抗白血病免疫和对免疫治疗（如 PD-1/PD-L1 抑制剂和抗-CD47 药物）的敏感性。本文描述了白血病微环境的免疫肿瘤学背景以及 HMAs 的治疗机制，以及目前关于 HMAs 和/或 venetoclax 联合治疗的临床试验。
