We identified a plethora of immune checkpoints (ICs) carried by the CLL-EVs (including the ectonucleotidases CD39 and CD73, PD-L1, TGFβ, the TIM3 ligand galectin-9, and the TIGIT ligand CD112) that could explain the observed effects on T-cells. Here, CD274 is linked to B-cell chronic lymphocytic leukemia.