Alfa-mannosidase inhibitor effect, Swainsonina, on the phenotype of tumor associated macrophages

• Grant number: 16/16149-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2016
• Effective date (End): November 30, 2018
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Ana Paula Lepique
• Grantee: Marcella Cipelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Infection with human papillomavirus (HPV) is the main etiologic factor of cervical cancer, as well as other anogenital and oropharyngeal tumors. Despite our body being able to recognize and eliminate these viruses, HPV have several escape mechanisms of the immune response, reaching remain decades in some infected individuals. In such cases, cells infected with HPV purchase: resistance to apoptosis, independent of mitogenic signals, the potential for unlimited proliferation, angiogenesis, and evasion of the immune response to the development of an invasive carcinoma. During this process, the immune system plays an important role, but not fully established. It is known, for example, the number of infiltrating macrophages increase in proportion to the degree of the lesion, with a maximum of cancer. Our laboratory and others have shown that tumor associated macrophages facilitate tumor growth. Swainsonine is an enzyme that specifically inhibits the enzyme alpha-mannosidase family, expressed by both tumor cells and by macrophages. Our laboratory identified this enzyme as a potential therapeutic target, using the methodology of "peptide phage display" with tumor lines derived from cervical cancer. Treatment of mice with partially Swainsonine inhibits tumor growth by promoting reduction of expression of arginase, an M2 type macrophage marker. In order to determine if inhibition of alpha-mannosidase has a direct effect on the phenotype of macrophages associated with tumors, this project will investigate the effect of treatment with Swainsonine on the phenotype of isolated tumor macrophages, and on their ability to activate T lymphocytes.

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)

ROSSETTI, RENATA A. M.; DA SILVA-JUNIOR, ILDEFONSO A.; R RODRIGUEZ, GRETEL; ALVAREZ, KARLA L. F.; STONE, SIMONE C.; CIPELLI, MARCELLA; SILVEIRA, CAIO R. F.; BELDI, MARIANA CARMEZIM; MOTA, GIANA R.; MARGARIDO, PAULO F. R.; et al. Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer. FRONTIERS IN ONCOLOGY, v. 10, NOV 19 2020. (14/19326-6, 13/26856-9, 16/16149-1, 18/16989-5, 11/20499-4)