BACKGROUND Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized. METHODS In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples. RESULTS We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival. CONCLUSIONS Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.

中文翻译：

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小儿和成人急性髓细胞性白血病的免疫受体库。

背景技术由血液或骨髓中的未成熟骨髓细胞的异常增殖引起的急性骨髓性白血病（AML）是最常见的血液系统恶性肿瘤之一。目前，恶性骨髓细胞与免疫微环境，特别是T细胞和B细胞之间的相互作用仍然很差。方法在这项研究中，我们从145例儿科和151例成人AML样本以及73例非肿瘤性外周血样本的RNA-seq数据中系统地分析了T细胞受体和B细胞受体（TCR和BCR）的组成。结果我们推断TCRα，β，γ和δ链中超过225,000个互补决定区3（CDR3）序列，以及B细胞免疫球蛋白（Ig）重链和轻链中的1,210,000 CDR3序列。我们发现在AML微环境中T细胞和B细胞均有更高的克隆扩增，并观察到儿科和成人AML之间存在许多差异。最值得注意的是，与儿童AML或非肿瘤样本相比，成人AML样本具有显着更高的B细胞活化水平和更多的继发性Ig类转换事件。此外，具有高度扩展的IgA2 B细胞的成年AML（可能代表一种免疫抑制的微环境）与调节性T细胞和较差的总体存活率有关。结论我们对AML免疫受体库的全面表征提高了我们对AML中T细胞和B细胞免疫的认识，这可能为血液恶性肿瘤的免疫治疗提供了见识。与儿童AML或非肿瘤样本相比，成人AML样本具有显着更高的B细胞活化水平和更多的继发性Ig类转换事件。此外，具有高度扩展的IgA2 B细胞的成年AML（可能代表一种免疫抑制的微环境）与调节性T细胞和较差的总体存活率有关。结论我们对AML免疫受体库的全面表征改善了我们对AML中T细胞和B细胞免疫的了解，这可能为血液恶性肿瘤的免疫治疗提供了见识。与儿童AML或非肿瘤样本相比，成人AML样本具有显着更高的B细胞活化水平和更多的继发性Ig类转换事件。此外，具有高度扩展的IgA2 B细胞的成年AML（可能代表一种免疫抑制的微环境）与调节性T细胞和较差的总体存活率有关。结论我们对AML免疫受体库的全面表征提高了我们对AML中T细胞和B细胞免疫的认识，这可能为血液恶性肿瘤的免疫治疗提供了见识。与调节性T细胞和较差的整体存活率有关。结论我们对AML免疫受体库的全面表征改善了我们对AML中T细胞和B细胞免疫的了解，这可能为血液恶性肿瘤的免疫治疗提供了见识。与调节性T细胞和较差的整体存活率有关。结论我们对AML免疫受体库的全面表征提高了我们对AML中T细胞和B细胞免疫的认识，这可能为血液恶性肿瘤的免疫治疗提供了见识。