Large-scale single-cell dissection of immune dysregulation in patients with monoclonal gammopathies

differences could be observed on SPECT/CT images of naïve and MM mice, ex vivo biodistribution analysis showed a significant uptake and increase of anti-LAG-3 nanobodies in the bone and spleen at 14 DPI (20-40% tumor load) and 21 DPI (60-80% tumor load) compared to naïve mice.Within the CD45+ population in the spleen, we observed an increase in neutrophils (CD11b+Ly6G+) and monocytes (CD11b+Ly6G) during MM disease progression.In the bone marrow (BM), we observed a significant increase in CD4+ T-cells and CD8+ T-cells at 14 DPI and 21 DPI within the CD45+ cell fraction.Flow cytometry analysis revealed a significant higher LAG-3 expression on MM cells upon disease progression.Within the lymphoid population, LAG-3 expression was increased in BMderived CD8+ T-cells, while this remained unaffected in splenic T-cells.LAG-3 expression generally decreased in almost all myeloid subsets (e.g.macrophages, dendritic cells (DCs)), except splenic monocytes and plasmacytoid DCs, during MM disease progression.Conclusions: Ex vivo biodistribution data revealed increased LAG-3 expression and nanobody uptake in MM-infiltrating organs.Using flow cytometry, a high expression of LAG-3 was observed in MM cells and lymphoid cells, which significantly increased within BMderived CD8+ T-cells at end-stage of disease.Altogether, these data illustrate increased expression of LAG-3 upon disease progression and fosters the evaluation of LAG-3 blocking therapies, particularly in the context of immunotherapeutic approaches in MM.