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Immunogenomic Landscape of Hematological Malignancies

机译：血液天动学恶性肿瘤的免疫因素景观

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摘要

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.
机译：了解影响血液系统恶性肿瘤免疫景观的因素对于免疫治疗的发展至关重要。我们将8000多个转录组和2000个样本与血液系统癌症的多水平基因组学进行整合，以研究免疫学特征如何与癌症亚型、遗传和表观遗传学改变以及患者存活率相关，并通过实验验证了关键发现。细胞毒性淋巴细胞浸润与急性髓系白血病中TP53和骨髓发育不良相关的改变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，如髓系恶性肿瘤中的VISTA，以及癌症抗原表达的变异进一步促进了免疫异质性和预测生存率。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。

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  • 来源
    《Cancer Cell》 |2020年第3期|共33页
  • 作者

    Dufva Olli; Polonen Petri; Bruck Oscar; Keranen Mikko Ai; Klievink Jay; Mehtonen Juha; Huuhtanen Jani; Kumar Ashwini; Malani Disha; Siitonen Sanna; Kankainen Matti; Ghimire Bishwa; Lahtela Jenni; Mattila Pirkko; Vaha-Koskela Markus; Wennerberg Krister; Granberg Kirsi; Leivonen Suvi-Katri; Meriranta Leo; Heckman Caroline; Leppa Sirpa; Nykter Matti; Lohi Olli; Heinaniemi Merja; Mustjoki Satu;

  • 作者单位

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Univ Eastern Finland Sch Med Inst Biomed Kuopio 70211 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Univ Eastern Finland Sch Med Inst Biomed Kuopio 70211 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    UH &

    HUSLAB Dept Clin Chem HUH Helsinki 00029 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Inst Mol Med Finland UH Helsinki 00014 Finland;

    Tampere Univ TU Fac Med &

    Hlth Technol Lab Computat Biol Tampere 33014 Finland;

    HUH CCC Dept Oncol Helsinki 00029 Finland;

    HUH CCC Dept Oncol Helsinki 00029 Finland;

    iCAN Digital Precis Canc Med Flagship Helsinki Finland;

    iCAN Digital Precis Canc Med Flagship Helsinki Finland;

    Tampere Univ TU Fac Med &

    Hlth Technol Lab Computat Biol Tampere 33014 Finland;

    Tampere Univ Hosp Tampere Ctr Child Hlth Res TU &

    Tays Canc Ctr Tampere 33521 Finland;

    Univ Eastern Finland Sch Med Inst Biomed Kuopio 70211 Finland;

    Univ Helsinki Hosp Comprehens Canc Ctr HUH CCC Hematol Res Unit Helsinki Helsinki 00029 Finland;

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  • 正文语种 eng
  • 中图分类 肿瘤学;
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