Gurska Lindsay, Gritsman Kira
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cancer Drug Resist. 2023 Sep 26;6(3):674-687. doi: 10.20517/cdr.2023.39. eCollection 2023.
Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy that is associated with a high relapse rate and poor prognosis. Despite advances in immunotherapies in solid tumors and other hematologic malignancies, AML has been particularly difficult to treat with immunotherapies, as their efficacy is limited by the ability of leukemic cells to evade T cell recognition. In this review, we discuss the common mechanisms of T cell evasion in AML: (1) increased expression of immune checkpoint molecules; (2) downregulation of antigen presentation molecules; (3) induction of T cell exhaustion; and (4) creation of an immunosuppressive environment through the increased frequency of regulatory T cells. We also review the clinical investigation of immune checkpoint inhibitors (ICIs) in AML. We discuss the limitations of ICIs, particularly in the context of T cell evasion mechanisms in AML, and we describe emerging strategies to overcome T cell evasion, including combination therapies. Finally, we provide an outlook on the future directions of immunotherapy research in AML, highlighting the need for a more comprehensive understanding of the complex interplay between AML cells and the immune system.
急性髓系白血病(AML)是一种异质性且侵袭性的血液系统恶性肿瘤,与高复发率和不良预后相关。尽管实体瘤和其他血液系统恶性肿瘤的免疫疗法取得了进展,但AML一直特别难以用免疫疗法治疗,因为白血病细胞逃避T细胞识别的能力限制了其疗效。在这篇综述中,我们讨论了AML中T细胞逃避的常见机制:(1)免疫检查点分子表达增加;(2)抗原呈递分子下调;(3)T细胞耗竭的诱导;以及(4)通过调节性T细胞频率增加创造免疫抑制环境。我们还综述了AML中免疫检查点抑制剂(ICI)的临床研究。我们讨论了ICI的局限性,特别是在AML的T细胞逃避机制背景下,并描述了克服T细胞逃避的新兴策略,包括联合疗法。最后,我们展望了AML免疫治疗研究的未来方向,强调需要更全面地了解AML细胞与免疫系统之间复杂的相互作用。
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