Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center (HUH CCC), 00029 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki (UH), 00029 Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland.
Institute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Cancer Cell. 2020 Sep 14;38(3):380-399.e13. doi: 10.1016/j.ccell.2020.06.002. Epub 2020 Jul 9.
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-γ 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.
了解影响血液恶性肿瘤免疫景观的因素对于免疫疗法的发展至关重要。我们整合了超过 8000 个转录组和 2000 个样本的血液癌症多层次基因组学数据，以研究免疫特征如何与癌症亚型、遗传和表观遗传改变以及患者生存相关，并通过实验验证了关键发现。在急性髓系白血病中，细胞毒性淋巴细胞的浸润与 TP53 和骨髓增生异常相关改变有关，而在淋巴瘤中则与激活的 B 细胞样表型和干扰素-γ反应有关。CIITA 甲基化调节抗原呈递、癌症类型特异性免疫检查点（如髓系恶性肿瘤中的 VISTA）以及癌症抗原表达的变异进一步导致了免疫异质性并预测了生存。我们的研究提供了一个资源，将免疫学与血液恶性肿瘤中的癌症亚型和基因组学联系起来。
