Unveiling T cell evasion mechanisms to immune checkpoint inhibitors in acute myeloid leukemia.
Unveiling T cell evasion mechanisms to immune checkpoint inhibitors in acute myeloid leukemia.
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DOI：
10.20517/cdr.2023.39
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发表时间：
2023
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急性髓系白血病（AML）是一种异质性、侵袭性血液系统恶性肿瘤，复发率高，预后不良。尽管实体瘤和其他血液恶性肿瘤的免疫疗法取得了进展，但用免疫疗法治疗 AML 特别困难，因为其疗效受到白血病细胞逃避 T 细胞识别的能力的限制。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)抗原呈递分子的下调； (3)诱导T细胞耗竭； (4) 通过增加调节性 T 细胞的频率来创建免疫抑制环境。我们还回顾了免疫检查点抑制剂 (ICIs) 在 AML 中的临床研究。我们讨论了 ICI 的局限性，特别是在 AML 中 T 细胞逃避机制的背景下，我们描述了克服 T 细胞逃避的新兴策略，包括联合疗法。最后，我们对 AML 免疫治疗研究的未来方向进行了展望，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。
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.