Abstract:
: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.
journal_name
J Biotechnoljournal_title
Journal of biotechnologyauthors
Rodet F,Capuz A,Hara T,van Meel R,Duhamel M,Rose M,Raffo-Romero A,Fournier I,Salzet Mdoi
10.1016/j.jbiotec.2018.07.002subject
Has Abstractpub_date
2018-09-20 00:00:00pages
80-85eissn
0168-1656issn
1873-4863pii
S0168-1656(18)30528-5journal_volume
282pub_type
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