Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14 968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. We show that the HERV retrotranscriptome accurately characterizes normal and leukemic cell subpopulations, including leukemia stem cells, in line with different epigenetic profiles. We then show that HERV expression delineates AML subtypes with different prognoses. We finally propose a method to select and prioritize CD8⁺ T cell epitopes derived from AML-specific HERVs and we show that lymphocytes infiltrating patient bone marrow at diagnosis contain naturally occurring CD8⁺ T cells against these HERV epitopes. We also provide in vitro data supporting the functionality of HERV-specific CD8⁺ T-cells against AML cells. These results show that HERVs represent an important source of genetic information that can help enhancing disease stratification or biomarker identification and an important reservoir of alternative tumor-specific T cell epitopes relevant for cancer immunotherapy.

中文翻译：

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HERV 表征正常和白血病干细胞，代表癌症免疫治疗的共享表位来源

人类内源性逆转录病毒 (HERV) 占人类基因组的 8%。HERV 的表达及其免疫影响尚未在急性髓性白血病 (AML) 中得到广泛研究。在这项研究中，我们使用了 14 968 个 HERV 功能单元的参考来提供对正常和 AML 骨髓细胞中 HERV 表达的全面分析。我们表明 HERV 逆转录组准确地表征了正常和白血病细胞亚群，包括白血病干细胞，符合不同的表观遗传特征。然后我们表明 HERV 表达描绘了具有不同预后的 AML 亚型。我们最终提出了一种方法来选择和优先考虑源自 AML 特异性 HERV 的CD8 ^{+ T 细胞表位，并且我们表明在诊断时浸润患者骨髓的淋巴细胞含有天然存在的 CD8+}针对这些 HERV 表位的 T 细胞。我们还提供支持 HERV 特异性 CD8 ⁺ T 细胞对抗 AML 细胞功能的体外数据。这些结果表明，HERV 代表了一种重要的遗传信息来源，可以帮助增强疾病分层或生物标志物鉴定，并且是与癌症免疫治疗相关的替代肿瘤特异性 T 细胞表位的重要储存库。