Deciphering molecular consequences of the proprotein convertase 1/3 inhibition in macrophages for application in anti-tumour immunotherapy

作者：Rodet Franck^*; Capuz Alice; Hara Tsukasa; van Meel Rinaldo; Duhamel Marie; Rose Melanie; Raffo Romero Antonella; Fournier Isabelle; Salzet Michel

来源：Journal of Biotechnology, 2018, 282: 80-85.

DOI：10.1016/j.jbiotec.2018.07.002

• Proprotein convertase PC1/3
• TLR4
• TLR9
• Macrophages
• Anti-tumour effect
• Cell therapy

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.

• 出版日期2018-9-20