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Peptides are molecules that have emerged as crucial candidates for the development of anticancer drugs. Spider venoms are a rich source of peptides (venom peptides - VPs) with biological effects. VPs have been tested as adjuvants in the activation of cells of the immune system with the aim of improving immunotherapies for the treatment of neoplasms. In the present study, the effects of SNX-482, a peptide from the African tarantula Hysterocrates gigas, on macrophages were described. The results showed that the peptide activated M0-macrophages, increasing costimulatory molecules (CD40, CD68, CD80, CD83, CD86) involved in antigen presentation, and also augmenting the checkpoint molecules PD-L1, CTLA-4 and FAS-L; these effects were not concentration-dependent. SNX-482 also increased the release of IL-23 and upregulated the expression of ccr4, ifn-g, gzmb and pdcd1, genes important for the anticancer response. The pretreatment of macrophages with the peptide did not interfere in the modulation of T cells, and macrophages previously polarized to M1 and M2 profile did not respond to SNX-482. These findings represent the expansion of knowledge about the use of VPs in drug discovery, pointing to a potential new candidate for anticancer immunotherapy. Considering that most immunotherapies target the adaptive system, the modulation of macrophages (an innate immune cell) by SNX-482 is especially relevant., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)