Immunogenomic Landscape of Hematological Malignancies
Immunogenomic Landscape of Hematological Malignancies
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DOI：
10.1016/j.ccell.2020.06.002
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发表时间：
2020-09-14
期刊：
影响因子：
50.3
通讯作者：
Mustjoki, Satu
中科院分区：
文献类型：
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作者：
Dufva, Olli;Polonen, Petri;Mustjoki, Satu
了解影响血液恶性肿瘤免疫格局的因素对于免疫疗法的开发至关重要。我们将8,000多个转录组和2,000个样本与血液癌症的多层次基因组学相结合，以研究免疫学特征如何与癌症亚型、遗传和表观遗传改变以及患者生存率相关联，并通过实验验证了关键发现。细胞毒性淋巴细胞的浸润与急性髓性白血病中TP 53和骨髓增生异常相关的变化以及淋巴瘤中活化的B细胞样表型和干扰素-γ反应相关。CIITA甲基化调节抗原呈递、癌症类型特异性免疫检查点（如骨髓恶性肿瘤中的VISTA）和癌症抗原表达的变化进一步促进了免疫异质性和预测的存活率。我们的研究提供了一个资源，将免疫学与恶性血液病的癌症亚型和基因组学联系起来。
Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-gamma response in lymphoma. CIITA methylation regulating antigen presentation, cancer type-specific immune checkpoints, such as VISTA in myeloid malignancies, and variation in cancer antigen expression further contributed to immune heterogeneity and predicted survival. Our study provides a resource linking immunology with cancer subtypes and genomics in hematological malignancies.