R. Ostuni, F. Kratochvill, P. J. Murray, and G. Natoli, Macrophages and cancer: from mechanisms to therapeutic implications, Trends Immunol, vol.36, pp.229-239, 2015.

J. Pohar, A. Kuznik-krajnik, R. Jerala, and M. Bencina, Minimal sequence requirements for oligodeoxyribonucleotides activating human TLR9, J Immunol, vol.194, pp.3901-3908, 2015.

J. M. Rodriguez, PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colonystimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells, PLoS One, vol.10, p.117484, 2015.

Y. H. Kim, In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study, Blood, vol.119, pp.355-363, 2012.

Y. Shirota, H. Shirota, and D. M. Klinman, Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells, J Immunol, vol.188, pp.1592-1599, 2012.

B. G. Molenkamp, Local administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell reactivity in melanoma patients, Clin Cancer Res, vol.14, pp.4532-4542, 2008.

J. D. Brody, In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study, J Clin Oncol, vol.28, pp.4324-4332, 2010.

M. A. Hofmann, Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma, Journal of immunotherapy, vol.31, pp.520-527, 2008.

A. Chockalingam, J. C. Brooks, J. L. Cameron, L. K. Blum, and C. A. Leifer, TLR9 traffics through the Golgi complex to localize to endolysosomes and respond to CpG DNA, Immunology and cell biology, vol.87, pp.209-217, 2009.

E. Latz, TLR9 signals after translocating from the ER to CpG DNA in the lysosome, Nat Immunol, vol.5, pp.190-198, 2004.

Y. M. Kim, M. M. Brinkmann, M. E. Paquet, and H. L. Ploegh, UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes, Nature, vol.452, pp.234-238, 2008.

K. Takahashi, A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses, J Exp Med, vol.204, pp.2963-2976, 2007.

S. Demoulin, HMGB1 secretion during cervical carcinogenesis promotes the acquisition of a tolerogenic functionality by plasmacytoid dendritic cells, Int J Cancer, 2014.

J. C. Brooks, W. Sun, G. Chiosis, and C. A. Leifer, Heat shock protein gp96 regulates Toll-like receptor 9 proteolytic processing and conformational stability, Biochem Biophys Res Commun, vol.421, pp.780-784, 2012.

J. E. Park, Y. I. Kim, and A. K. Yi, Protein kinase D1: a new component in TLR9 signaling, J Immunol, vol.181, pp.2044-2055, 2008.

M. Yoshizaki, Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q, Blood, vol.114, pp.1518-1527, 2009.

M. Duhamel, Molecular consequences of proprotein convertase 1/3 inhibition in macrophages for application to cancer immunotherapy: a proteomic study, Mol Cell Proteomics, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01850616

S. Refaie, Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion, J Biol Chem, vol.287, pp.14703-14717, 2012.

H. Gagnon, Proprotein convertase 1/3 (PC1/3) in the rat alveolar macrophage cell line NR8383: localization, trafficking and effects on cytokine secretion, PLoS One, vol.8, p.61557, 2013.

, Scientific RepoRts |, vol.6, 19360.

D. Moreira, TLR9 signaling through NF-kappaB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells, Oncotarget, vol.6, pp.17302-17313, 2015.

M. Kortylewski, Toll-like receptor 9 activation of signal transducer and activator of transcription 3 constrains its agonist-based immunotherapy, Cancer Res, vol.69, pp.2497-2505, 2009.

C. St-germain, Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development. Molecular reproduction and development 72, pp.483-493, 2005.

B. Manoury, TLR9 regulation by proteolysis: a friend or a foe, Eur J Immunol, vol.41, pp.2142-2144, 2011.

A. F. Carpentier, Cancer immunotherapy with CpG-ODN

, Med Sci (Paris), vol.21, pp.73-77, 2005.

S. E. Ewald and G. M. Barton, Nucleic acid sensing Toll-like receptors in autoimmunity, Current opinion in immunology, vol.23, pp.3-9, 2011.

S. E. Ewald, The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor, Nature, vol.456, pp.658-662, 2008.

S. E. Ewald, Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase, J Exp Med, vol.208, pp.643-651, 2011.

F. E. Sepulveda, Critical role for asparagine endopeptidase in endocytic Toll-like receptor signaling in dendritic cells, Immunity, vol.31, pp.737-748, 2009.

B. Park, Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9, Nat Immunol, vol.9, pp.1407-1414, 2008.

M. M. Hipp, Processing of human toll-like receptor 7 by furin-like proprotein convertases is required for its accumulation and activity in endosomes, Immunity, vol.39, pp.711-721, 2013.

T. Kimura, Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses, J Immunol, vol.194, pp.5426-5436, 2015.

B. L. Lee, UNC93B1 mediates differential trafficking of endosomal TLRs, vol.2, p.291, 2013.

T. A. Chen, Stimulation of Proliferation and Migration of Mouse Macrophages by Type B CpG-ODNs Is F-Spondin and IL-1Ra Dependent, PLoS One, vol.10, p.128926, 2015.

H. H. Ho and L. B. Ivashkiv, Role of STAT3 in type I interferon responses. Negative regulation of STAT1-dependent inflammatory gene activation, J Biol Chem, vol.281, pp.14111-14118, 2006.

M. Kortylewski and S. K. Pal, The dark side of Toll-like receptor signaling: TLR9 activation limits the efficacy cancer radiotherapy, Oncoimmunology, vol.3, p.27894, 2014.

E. S. Reynolds, The use of lead citrate at high pH as an electron-opaque stain in electron microscopy, J Cell Biol, vol.17, pp.208-212, 1963.

G. Griffiths, K. Simons, G. Warren, and K. T. Tokuyasu, Immunoelectron microscopy using thin, frozen sections: application to studies of the intracellular transport of Semliki Forest virus spike glycoproteins, Methods Enzymol, vol.96, pp.466-485, 1983.