| Literature DB >> 32649887 |
Olli Dufva1, Petri Pölönen2, Oscar Brück1, Mikko A I Keränen3, Jay Klievink3, Juha Mehtonen2, Jani Huuhtanen3, Ashwini Kumar4, Disha Malani4, Sanna Siitonen5, Matti Kankainen1, Bishwa Ghimire4, Jenni Lahtela4, Pirkko Mattila4, Markus Vähä-Koskela4, Krister Wennerberg4, Kirsi Granberg6, Suvi-Katri Leivonen7, Leo Meriranta7, Caroline Heckman8, Sirpa Leppä9, Matti Nykter6, Olli Lohi10, Merja Heinäniemi11, Satu Mustjoki12.
Abstract
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.Entities:
Keywords: antigen presentation; cancer; epigenomics; genomics; hematology; immune checkpoint; immunology; immunotherapy; leukemia; lymphoma
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Year: 2020 PMID： 32649887 DOI： 10.1016/j.ccell.2020.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743