Components From Spider Venom Activate Macrophages Against Glioblastoma Cells: New Potential Adjuvants for Anticancer Immunotherapy Publisher Pubmed



Munhoz J¹ ; Peron G² ; Bonfanti AP^{1, 2} ; Oliveira J² ; Da Rochaesilva TAA³ ; Sutti R⁴ ; Thome R^{2, 5} ; Bombeiro AL² ; Barreto N^{1, 2} ; Chalbatani GM⁶ ; Gharagouzloo E⁷ ; Vitorinoaraujo JL⁸ ; Verinaud L² ; Raposo C¹ Show Affiliations
Source: Journal of Biochemistry Published:2021

Abstract

Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model. The hypothesis that PnV would be modulating the innate immune system led us to the main objective of the present study: To elucidate the effects of PnV and its purified fractions on cultured macrophages. Results showed that PnV and the three fractions activated macrophages differentiated from bone marrow precursors. Further purification generated 23 subfractions named low weight (LW-1 to LW-12) and high weight (HW-1 to HW-11). LW-9 presented the best immunomodulatory effect. Treated cells were more phagocytic, migrated more, showed an activated morphological profile and induced an increased cytotoxic effect of macrophages on tumour cells. However, while M1-controls (LPS) increased IL-10, TNF-Alpha and IL-6 release, PnV, fractions and subfractions did not alter any cytokine, with the exception of LW-9 that stimulated IL-10 production. These findings suggest that molecules present in LW-9 have the potential to be used as immunoadjuvants in the treatment of cancer. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.