Summary

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.

Overall design

We integrated over 8,000 transcriptomes and over 2,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. For more detailed follow-up analyses in acute myeloid leukemia (AML), single-cell RNA sequencing was performed on 8 AML bone marrow samples at diagnosis to profile the phenotypes of blasts and infiltrating immune cells in different disease subtypes.

Contributors

Olli Dufva 1, Petri Pölönen 2, Oscar Brück 1, Mikko A I Keränen 3, Jay Klievink 3, Juha Mehtonen 2, Jani Huuhtanen 3, Ashwini Kumar 4, Disha Malani 4, Sanna Siitonen 5, Matti Kankainen 1, Bishwa Ghimire 4, Jenni Lahtela 4, Pirkko Mattila 4, Markus Vähä-Koskela 4, Krister Wennerberg 4, Kirsi Granberg 6, Suvi-Katri Leivonen 7, Leo Meriranta 7, Caroline Heckman 8, Sirpa Leppä 9, Matti Nykter 6, Olli Lohi 10, Merja Heinäniemi 11, Satu Mustjoki 12

Contact

satu.mustjoki@helsinki.fi.(Satu Mustjoki)