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Molecular markers of tumorigenesis and immune evasion during the natural history of cervical cancer

Grant number: 19/26558-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Ana Paula Lepique
Grantee:Emily Cabral Dacol
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Our laboratory has been working on characterizing the interactions between tumor and immune system cells in the tumor microenvironment. Our main target has been cervical tumors, for which the main etiological factor is persistent high-risk oncogenic human papillomavirus (HPV) infection. We have described the role of interactions between tumor cells and immune system cells, involving the secretion of lactate and cytokines by tumor cells and triggering a tolerogenic phenotype in cells of the immune system. This project aims to study, through immunohistochemistry, the expression of molecular markers of tumorigenesis associated with HPV infection, which were previously described and studied by the laboratory, in tissues of patients with cervicitis, grades 1 to 3 intraepithelial neoplasia and cervical cancer. We will study the localization of leukocyte populations in lesions and tumors, as well as the expression of STAT3, p65 NFkB, and Akt proteins, which expression in cervical lesions was previously characterized by the laboratory. In addition, we intend to test the hypothesis that SET, a protein we found differentially expressed in cells expressing HPV oncogenes, is involved in the metabolic regulation of cervical cancer cells. The immunohistochemistry assays will allow us to confirm and investigate the level of protein expression in the different cell populations of the tumor microenvironment and to verify the subcellular localization of the proteins of interest. This study is essential, as previous studies were based on flow cytometry or Western blotting, which destroys the tissue. The study of factors such as those described above has potential prognostic importance and search for therapeutic tools. (AU)