Immune landscape of haematological cancers mapped

A major new analysis has revealed the immune landscape of haematological cancers, which could lead to better immunotherapies and identify patients for whom these therapies may have significant impact.

Researchers at the University of Helsinki, Helsinki University Hospital and the University of Eastern Finland used datasets covering more than 10,000 patients with a range of haematological malignancies. Their aim was to understand how the responsiveness of cancers to immune therapies might vary, and identify the molecular mechanisms behind this.

Based on the findings, cytotoxic T and NK cells were found to be abundant in certain subtypes of cancer, such as activated B cell-like B cell lymphoma and acute myeloid leukaemia (AML). Previous research from solid tumours suggests that high infiltration by these killer T cells and NK cells is associated with a good response to immunotherapy.

Very high numbers of cancer-germline antigens were found to be expressed in multiple myeloma, which can potentially be used as vaccine or cell therapy targets.

The researchers also found that in certain subtypes of AML, antigen presentation had been epigenetically silenced by DNA methylation. The team found that a drug inhibiting DNA methylation, decitabine, restored the expression of antigen-presenting proteins in laboratory test with cell lines. Because decitabine is already used to treat AML, the researchers say it could be combined with immunotherapies to increase their efficiency.

The research, published in Cancer Cell, was jointly led by Associate Professor Merja Heinäniemi from the University of Eastern Finland and Professor Satu Mustjoki from the University of Helsinki.

Associate Professor Heinäniemi said: “Key to the study was the integration of immunology and applied computational analysis. With the help of innovative analysis methods, we were able to correlate molecular features of haematological malignancies with the activity of different immune cells.”

Professor Mustjoki added: “The extensive survey of the immunogenomic features of haematological malignancies carried out in the study helps scientists and doctors target immunotherapies at the patient groups that gain the most benefit as well as understand the factors that have a potential impact on the efficacy of therapies.”

Source: Dufva O, Pölönen P, Brück O, Keränen MAI, Klievink J, Mehtonen J, Huuhtanen J, Kumar A, Malani D, Siitonen S, Kankainen M, Ghimire B, Lahtela J, Mattila P, Vähä-Koskela M, Wennerberg K, Granberg K, Leivonen S-K, Meriranta L, Heckman C, Leppä S, Nykter M, Lohi O, Heinäniemi M, Mustjoki S. (2020) “Immunogenomic Landscape of Hematological Malignancies”, Cancer Cell, doi: 10.1016/j.ccell.2020.06.002