Deciphering Molecular Consequences of the Proprotein Convertase 1/3 Inhibition in Macrophages for Application in Anti-tumour Immunotherapy

Publication date: Available online 7 July 2018Source: Journal of BiotechnologyAuthor(s): Franck Rodet, Alice Capuz, Tsukasa Hara, Rinaldo van Meel, Marie Duhamel, Mélanie Rose, Antonella Raffo Romero, Isabelle Fournier, Michel SalzetAbstractDuring tumour development, macrophages are recruited to the tumour site and orientated towards an anti-inflammatory phenotype. Due to their immunosuppressive function, tumour associated macrophages (TAMs) are recognized as major components in tumour progression. Changing these macrophages to a pro-inflammatory phenotype is thus extensively studied as a potential means for developing novel anti-tumour therapy. In this context, we found that the Proprotein convertase 1/3 (PC1/3) is a relevant target. Proteomic analysis reveals that PC1/3 knockdown (KD) macrophages present all the characteristic of activated pro-inflammatory macrophages. Moreover, in PC1/3 KD macrophages, TLR4 and TLR9 signaling pathways can be enhanced leading to the secretion of pro-inflammatory factors and anti-tumour factors. To develop an efficient anti-tumour immunotherapy, we may (i) target TAMs directly inside the tumour site for PC1/3 inhibition and TLR activation and used them as “Trojan macrophages” or (ii) directly take advantage of PC1/3 inhibited macrophages and use them as “drone macrophages” by activating them “at distance” with a TLR ligand. Therefore, PC1/3 inhibited macrophages constitute an innovative cell therapy to treat tumours efficiently.
Source: Journal of Biotechnology - Category: Biotechnology Source Type: research