Tsukasa HARA    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Deciphering molecular consequences of the proprotein convertase 1/3 inhibition in macrophages for application in anti-tumour immunotherapy.
Journal	Formal name：Journal of biotechnology Abbreviation：J Biotechnol ISSN code：18734863/01681656
Domestic / Foregin	Foregin
Volume, Issue, Page	282,pp.80-85
Total page number	6
Author and coauthor	Rodet Franck, Capuz Alice, Hara Tsukasa, van Meel Rinaldo, Duhamel Marie, Rose Mélanie, Raffo-Romero Antonella, Fournier Isabelle, Salzet Michel
Publication date	2018/09
Summary	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.
DOI	10.1016/j.jbiotec.2018.07.002
PMID	29990570