ハラ ツカサ   Hara Tsukasa
  原 司
   所属   医学研究科 医学研究科 (医学部医学科をご参照ください)
   職種   特任助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Deciphering molecular consequences of the proprotein convertase 1/3 inhibition in macrophages for application in anti-tumour immunotherapy.
掲載誌名 正式名:Journal of biotechnology
略  称:J Biotechnol
ISSNコード:18734863/01681656
掲載区分国外
巻・号・頁 282,pp.80-85
総ページ数 6
著者・共著者 Rodet Franck, Capuz Alice, Hara Tsukasa, van Meel Rinaldo, Duhamel Marie, Rose Mélanie, Raffo-Romero Antonella, Fournier Isabelle, Salzet Michel
発行年月 2018/09
概要 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