Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy

Abstract

Immunomodulation has been considered an important approach in the treatment of malignant tumors. 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 tumor 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 twenty-three 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 tumor 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.

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

“…Glioblastoma resistance to bevacizumab occurs due to an immunosuppressive microenvironment triggered by VEGF ( Tamura et al, 2019 ). Thus, modulation of the immune response is the strategy of choice for malignant tumors such as glioblastoma ( Munhoz et al, 2021 ).…”

Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma

“…LW9 induced a balance between pro- and anti-inflammatory cytokine release and an activated morphology of DCs. We recently demonstrated that the same molecule, LW9, induced an activated profile of macrophages [ 16 ]. It has been shown that PnV is composed mainly of small proteins, enzymes and peptides [ 35 ].…”

“…These results lead us to investigate whether PnV components activate immune cells. A recent study demonstrated that, in fact, the venom induced a phagocytic and active macrophage profile [ 16 ]; however, there is no information so far concerning the effects of PnV on the adaptive immune system. In this sense, the present study aims to evaluate the effect of PnV and its purified components as adjuvants in the activation of DCs, focusing on the treatment of GB.…”

Bioactive peptides from venoms against glioma progression

“…The above-mentioned PnV fractions were found to increase the number of monocytes in the blood of xenogeneic mice and the number of macrophages infiltrating in the tumor ( 130 ). It was demonstrated that the PnV spider venom fraction LW-9 increased cytotoxic and phagocytic activity of macrophages by immunomodulation ( 59 ). It was suggested that macrophages were reeducated into a non-TAMs phenotype, resulting in enhanced destruction of cancer cells.…”