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

• Grant number: 19/03761-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 01, 2019
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Jaqueline de Lima Munhoz
• Supervisor: Abdolmohamad Rostami
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MUNHOZ, JAQUELINE; THOME, RODOLFO; ROSTAMI, ABDOLMOHAMAD; ISHIKAWA, LARISSA LUMI WATANABE; VERINAUD, LIANA; RAPOSO, CATARINA. The SNX-482 peptide from Hysterocrates gigas spider acts as an immunomodulatory molecule activating macrophages. Peptides, v. 146, DEC 2021. (18/03051-9, 19/03761-9)