Extracellular vesicles from Nurse-Like Cells and THP1-derived Type-2 macrophages transfer aggressiveness to chronic lymphocytic leukemia cells

Abstract The resistance of leukemic B cells to cell death is mainly associated with interactions within the tumor microenvironment, where they interact with various types of cells. Within this microenvironment, CLL B cells produce and bind cytokines, growth factors, and microvesicles. In the present study, extracellular vesicles (EVs) purified from nurse-like cells and M2-polarized THP1 cell (M2-THP1) cultures were added to CLL B cell cultures. The vesicles were rapidly internalized by B cells, leading to a decrease in spontaneous apoptosis and an increase in proliferation. Additionally, the vesicles induced an increase in the resistance of CLL B cells to Bruton kinase inhibitor Ibrutinib. A transcriptomic analysis showed an increase in the expression of anti-apoptotic gene Bcl-2 but not Mcl-1 and an increase in the expression of proliferation-inducing gene APRIL following treatment of CLL B cells with EVs derived from both NLCs and M2-THP1 cells. Meanwhile, an analysis of apoptotic protein markers revealed increased amounts of IGFBP-2, CD40, p53 and Bcl-2 following EVs treatment. Finally, exploration of EVs protein content by mass spectrometry revealed they carry various proteins involved in known oncogenic pathways and the RNAseq analysis of B CLL cells treated or not with NLCs EVs show various differentially expressed genes.