PMID- 29990570 OWN - NLM STAT- MEDLINE DCOM- 20181102 LR - 20181102 IS - 1873-4863 (Electronic) IS - 0168-1656 (Linking) VI - 282 DP - 2018 Sep 20 TI - Deciphering molecular consequences of the proprotein convertase 1/3 inhibition in macrophages for application in anti-tumour immunotherapy. PG - 80-85 LID - S0168-1656(18)30528-5 [pii] LID - 10.1016/j.jbiotec.2018.07.002 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Rodet, Franck AU - Rodet F AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. Electronic address: franck.rodet@univ-lille1.fr. FAU - Capuz, Alice AU - Capuz A AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Hara, Tsukasa AU - Hara T AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - van Meel, Rinaldo AU - van Meel R AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Duhamel, Marie AU - Duhamel M AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Rose, Melanie AU - Rose M AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Raffo-Romero, Antonella AU - Raffo-Romero A AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Fournier, Isabelle AU - Fournier I AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. FAU - Salzet, Michel AU - Salzet M AD - Inserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 Villeneuve D'Ascq, France. LA - eng PT - Journal Article DEP - 20180707 PL - Netherlands TA - J Biotechnol JT - Journal of biotechnology JID - 8411927 RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 9) RN - EC 3.4.21.93 (Proprotein Convertase 1) SB - IM MH - Animals MH - Humans MH - *Immunotherapy MH - Macrophages/*immunology MH - Neoplasms/*therapy MH - Proprotein Convertase 1/genetics/*immunology MH - Protein Transport MH - Signal Transduction MH - Toll-Like Receptor 4/immunology MH - Toll-Like Receptor 9/immunology OTO - NOTNLM OT - Anti-tumour effect OT - Cell therapy OT - Macrophages OT - Proprotein convertase PC1/3 OT - TLR4 OT - TLR9 EDAT- 2018/07/11 06:00 MHDA- 2018/11/06 06:00 CRDT- 2018/07/11 06:00 PHST- 2018/04/19 00:00 [received] PHST- 2018/06/29 00:00 [revised] PHST- 2018/07/01 00:00 [accepted] PHST- 2018/07/11 06:00 [pubmed] PHST- 2018/11/06 06:00 [medline] PHST- 2018/07/11 06:00 [entrez] AID - S0168-1656(18)30528-5 [pii] AID - 10.1016/j.jbiotec.2018.07.002 [doi] PST - ppublish SO - J Biotechnol. 2018 Sep 20;282:80-85. doi: 10.1016/j.jbiotec.2018.07.002. Epub 2018 Jul 7.