Deciphering molecular consequences of the proprotein convertase 1/3 inhibition in macrophages for application in anti-tumour immunotherapy.
During 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.
['Rodet|Franck|F|', 'Capuz|Alice|A|', 'Hara|Tsukasa|T|', 'van Meel|Rinaldo|R|', 'Duhamel|Marie|M|', 'Rose|Mélanie|M|', 'Raffo-Romero|Antonella|A|', 'Fournier|Isabelle|I|', 'Salzet|Michel|M|']
D000818:Animals D006801:Humans D007167:Immunotherapy D008264:Macrophages D009369:Neoplasms D045664:Proprotein Convertase 1 D021381:Protein Transport D015398:Signal Transduction D051197:Toll-Like Receptor 4 D051217:Toll-Like Receptor 9
Macrophages TLR4 TLR9 Cell therapy Anti-tumour effect Proprotein convertase PC1/3