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Effects of P. nigriventer spider venom and its purified toxins in reprogramming M1 and M2 macrophages

Grant number: 19/03761-9
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Catarina Raposo Dias Carneiro
Grantee:Jaqueline de Lima Munhoz
Supervisor abroad: Abdolmohamad Rostami
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Thomas Jefferson University (TJU), United States  
Associated to the scholarship:18/03051-9 - Identification of macrophages modulators molecules from spider venom: new perspectives for the treatment of cancer, BP.IC

Abstract

Immunomodulation has been considered an established antitumor approach, since immune cells, mainly macrophages, are involved in tumorigenesis. The tumor microenvironment infiltrating cells include regulatory lymphocytes and myeloid cells, represented by different populations of macrophages known as tumor-associated macrophages (TAMs). Although they show a complex phenotypic and behavioral variation, TAMs can be simplistically divided into two subtypes, M1 and M2. Canonically, M1 profile is associated with pro-inflammatory properties and anti-tumor effects, while M2 phenotype has anti-inflammatory properties that promotes tumor growth and resistance to therapy. Reprogramming TAMs from a M2 molecular signature to M1 phenotype is a strategy that is proposed to change the course of the anti-tumor immune response. However, it can cause adverse effects, such as inducing metastasis. Furthermore, increasing evidence suggests that both, M1 and M2, contribute for tumorigenesis and tumor cells migration/metastasis, and cytokines released by M1 macrophages appears to be involved in these effects. Results from the project developed in Brazil, related to this proposal, have demonstrated that the venom of Phoneutria nigriventer (PnV), a wandering spider from South America, is capable to activate macrophages. Macrophages with a profile M0 when treated with the venom and its isolated toxins showed a phagocyting phenotype, significantly more efficient in killing tumor cells than non-stimulated M0-macrophages. Interestingly, while lipopolysaccharide (LPS; a control of M1 profile) induced the release of large amounts of cytokines, PnV-stimulated macrophages did not produce significant quantities of pro- or anti-inflammatory cytokines, being therefore a phenotype different of M1. This peculiar profile induced by venom molecules can be an efficient strategy to fight tumors without stimulate cancer development. Considering these results, is the aim of the present project to investigate whether the venom and its isolated peptides could reprogram M1 and M2 cells (that are present in tumors stroma) to this PnV-activated profile, which could redirect the immune response against the tumor. It can be further used as an immunoadjuvant, giving an opportunity for the development of a potential new anticancer therapy. (AU)

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