Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T Cell Immunity.
Targeting the Immune Microenvironment in Acute Myeloid Leukemia: A Focus on T Cell Immunity.
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DOI：
10.3389/fonc.2018.00213
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发表时间：
2018
影响因子：
4.7
通讯作者：
Lind EF
中科院分区：
文献类型：
--
作者：
Lamble AJ;Lind EF
免疫疗法，如嵌合抗原受体T细胞、双特异性抗体和免疫检查点抑制剂，已成为治疗多种血液系统恶性肿瘤的有效手段。尽管免疫疗法令人兴奋，但目前还不可能预测哪些患者会有反应。在实体瘤中，免疫微环境的状态对免疫治疗的潜在反应提供了有价值的见解。我们对血液系统恶性肿瘤的免疫微环境知之甚少，但这种环境的特点可能会起到类似的预测作用。急性髓系白血病是成人最常见的血液系统恶性肿瘤，确诊后5 年存活率仅为25%。有证据表明，白血病细胞对免疫微环境的操纵可能在促进治疗抵抗和疾病复发方面发挥作用。此外，长期以来一直有证据表明，通过调节异基因骨髓移植后的免疫系统，AML可以被治愈，即使是在疾病风险最高的患者中也是如此。这些概念，加上与这种疾病相关的不良预后，鼓励了许多小组开始探索新的免疫疗法在AML中的应用。虽然这些疗法在急性髓细胞白血病的临床试验中的实施得到了临床前理论的支持，但围绕它们的有效性、耐受性和总体最佳方法仍然存在许多问题。在这篇综述中，我们讨论了AML内免疫微环境的已知情况，特别关注T细胞和检查点，以及它们对免疫治疗的影响。
Immunotherapies, such as chimeric antigen receptor T cells, bispecific antibodies, and immune checkpoint inhibitors, have emerged as promising modalities in multiple hematologic malignancies. Despite the excitement surrounding immunotherapy, it is currently not possible to predict which patients will respond. Within solid tumors, the status of the immune microenvironment provides valuable insight regarding potential responses to immune therapies. Much less is known about the immune microenvironment within hematologic malignancies but the characteristics of this environment are likely to serve a similar predictive role. Acute myeloid leukemia (AML) is the most common hematologic malignancy in adults, and only 25% of patients are alive 5 years following their diagnosis. There is evidence that manipulation of the immune microenvironment by leukemia cells may play a role in promoting therapy resistance and disease relapse. In addition, it has long been documented that through modulation of the immune system following allogeneic bone marrow transplant, AML can be cured, even in patients with the highest risk disease. These concepts, along with the poor prognosis associated with this disease, have encouraged many groups to start exploring the utility of novel immune therapies in AML. While the implementation of these therapies into clinical trials for AML has been supported by preclinical rationale, many questions still exist surrounding their efficacy, tolerability, and the overall optimal approach. In this review, we discuss what is known about the immune microenvironment within AML with a specific focus on T cells and checkpoints, along with their implications for immune therapies.
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影响因子：
64.5
作者：
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