Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.

急性髓细胞性白血病（AML）是一种分子和临床异质性血液恶性肿瘤。尽管免疫疗法可能是在AML患者中开发的一种有吸引力的方式，但是预测患者群体和将对免疫靶向反应的癌症类型的能力仍然有限。这项研究以高分辨率剖析了AML免疫结构的复杂性，并评估了其对治疗反应的影响。使用来自三个独立的儿童和成人队列的442个原代骨髓样本，我们定义了免疫浸润和免疫耗竭的疾病类别，并揭示了不同年龄组和分子疾病亚型的免疫基因表达的关键差异。干扰素（IFN）-γ相关的mRNA谱可预测化疗耐药以及氟替妥珠单抗免疫治疗对原发性难治性/复发性AML的反应。我们的微环境基因和蛋白质谱纲要提供了洞悉AML免疫生物学的见解，并可以为针对IFN-γ的主要AML亚型提供个性化的免疫疗法。