Davidson-Moncada Jan, Viboch Elena, Church Sarah E, Warren Sarah E, Rutella Sergio
MacroGenics Inc., Rockville, MD 20850, USA.
NanoString Technologies Inc., Seattle, WA 98109, USA.
Biomedicines. 2018 Nov 25;6(4):110. doi: 10.3390/biomedicines6040110.
Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50⁻70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies. However, durable responses have been observed in only a minority of patients, highlighting the need to gain insights into the molecular features that predict response and to also develop more effective and rational combination therapies that address mechanisms of immune evasion and resistance. We will review the state of knowledge of the immune landscape of AML and identify the broad opportunity to further explore this incompletely characterized space. Multiplexed, spatially-resolved immunohistochemistry, flow cytometry/mass cytometry, proteomic and transcriptomic approaches are advancing our understanding of the complexity of AML-immune interactions and are expected to support the design and expedite the delivery of personalized immunotherapy clinical trials.
急性髓系白血病（AML）是一种分子异质性血液系统恶性肿瘤，对治疗反应各异。复发性细胞遗传学异常和分子病变可识别出具有不同生存概率的AML患者亚组；然而，50%-70%的AML病例核型正常或风险不确定。因此，发现更好的临床成败生物标志物对于指导个体化治疗决策至关重要。利用程序性死亡-1（PD-1）导向的免疫检查点阻断（ICB）和其他免疫治疗药物激活免疫系统对抗癌症，是几种晚期恶性肿瘤的有效治疗选择。然而，只有少数患者观察到持久反应，这凸显了深入了解预测反应的分子特征以及开发更有效、更合理的联合治疗方法以解决免疫逃逸和耐药机制的必要性。我们将回顾AML免疫格局的知识现状，并确定进一步探索这个特征尚不完整领域的广阔机会。多重、空间分辨免疫组织化学、流式细胞术/质谱流式细胞术、蛋白质组学和转录组学方法正在增进我们对AML免疫相互作用复杂性的理解，并有望支持个性化免疫治疗临床试验的设计并加速其开展。
