Belgian researchers have unveiled the first ‘atlas’ of the multiple myeloma immune microenvironment in a mouse model.
The research team, based in Brussels, believe their work can help guide developers of new immunotherapies.
Their atlas is based on single cell RNA sequencing across stages of the disease, in an immunocompetent mouse model, and corroborated with similar data from human patient samples.
The work led to some general discoveries about the immune microenvironment of the disease, finding an increase in T cells, especially in an ‘exhausted’ state. Early in the disease, neutrophils appeared “innocuous” but acquired cancer-triggering characteristics during the development of the disease. The researchers also found that conventional dendritic cells were underactive in the disease, leading them to test treatments to stimulate these cells.
Their work has been reported in the Journal of Hematology & Oncology and is being made freely available to research teams.
Researcher Dr Kim De Veirman said: “Our novel tool revealed conventional dendritic cells as a targetable population in multiple myeloma. We therefore performed the first pre-clinical evaluation of the DC-activating αCD40 therapy on murine and human samples, and in the multiple myeloma mouse model. Administering αCD40 led to a successful cDC- and subsequent T-cell activation, and a significant short-term anti-tumour response.”
Fellow researcher Emma Verheye said: “After correlating immune changes observed in our murine dataset with those in human patients across various disease stages, we were able to validate the dynamic changes upon disease progression, demonstrating how accurately this mouse model represents the human condition.”
Source:
Verheye E, Kancheva D, Satilmis H, Vandewalle N, Fan R, Bardet PMR, Clappaert EJ, Verstaen K, De Becker A, Vanderkerken K, De Veirman K, Laoui D. (2024) “A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages.” Journal of Hematology & Oncology, 7 November 2024, doi: 10.1186/s13045-024-01629-3.
Link: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01629-3
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