Experimental study design. DLBCL cells are cultured for 48 h in media supplemented with ultracentrifugation EV-depleted FBS (UC-dFBS). Conditioned media is harvested, depleted from cells, and subjected to serial differential centrifugation to pellet dead cells and large microvesicles. Cleared media is ultracentrifugated originating first a crude EV fraction and further purified by floatation on sucrose cushion. The proteomic workflow includes EVs protein extraction, protein digestion with trypsin, LC-MSMS of peptides, and data analysis (figure made by BioRender, https://biorender.com/, accessed on 20 July 2021).