We demonstrated here thanks to proteomic, that proprotein convertase 1/3 knockdown macrophages present all the characteristic of activated pro-inflammatory macrophages. TLR4 and TLR9 signaling pathways can be enhanced leading to the secretion of pro-inflammatory factors and antitumor factors. We can control their activation by controlling one enzyme, PC1/3. In a tumor context, PC1/3 inhibition in macrophages may reactivate them and lead to a cytokine storm after stimulation "at distance" with a TLR ligand. Therefore, we name these proprotein convertase inhibited macrophages the "drone macrophages". They constitute an innovative cell therapy to treat efficiently tumors.
Keywords: CCL, chemokine (C–C motif) ligand; CXCL, chemokine (C–X–C motif) ligand; KD, knockdown; LPS, lipopolysaccharides; MVB, multivesicular bodies; NT, non-target; PC, proprotein convertase; TAM, tumor associated macrophages; TLR, toll like receptor.