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Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C) - stimulated macrophages

ABSTRACT: Macrophages plasticity is a key feature in cancer progression. Neoplastic cells can alter their immune functions and orient them into a pro-tumoral phenotype. In this context and based on our previous work, we developed a new therapeutic strategy to switch macrophages phenotype and reactivate their anti-tumoral functions. In this context, we previously showed a dual activity of a proprotein convertases inhibitor as anti-glioma drug and anti-tumoral macrophages’ reactivation drug. Proprotein convertases are proteases that cleave proteins into functional proteins. Several of their substrates are involved in tumorigenesis and immunosuppression. In this study, we decided to combine proprotein convertases inhibitor with Poly (I:C), a TLR3 ligand, to increase the anti-tumoral activity of macrophages. With mass spectrometry-based proteomics we could establish that a stimulation of macrophages with Poly (I:C) increased their secretion of pro-inflammatory cytokines and anti-tumoral factors. 3D invasion assay showed the efficacy of these anti-tumoral factors against mixed glioma cells and macrophages spheroids. Besides, immunofluorescence and proliferation assays showed an additive effect of the proprotein convertases inhibitor and the anti-tumoral factors secreted by Poly (I:C)-treated macrophages on both anti-glioma activity and macrophages anti-tumoral orientation leading to an innovative glioma therapy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cell Culture, Macrophage

DISEASE(S): Glioblastoma

SUBMITTER: Melanie Rose

LAB HEAD: Michel Salzet

PROVIDER: PXD020258 | Pride | 2021-09-23

REPOSITORIES: Pride

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