Cancer triggered immunomodulation mechanisms: tumor born elements and their local systemic effects

• Grant number: 22/10388-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Paula Lepique
• Grantee: Ana Paula Lepique
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Signals generated in the tumor microenvironment (TEM) are important for cell communication within the TME and systemically. STAT3 (Signal Transducer and Activator of Transcription 3) is considered an oncogene, with direct roles on tumor cells, promoting proliferation, survival, epithelial-mesenchymal transition, and with roles on the TME, mostly by promoting tolerogenic responses. Gynecological cancers, although diverse and with different etiologies, display aberrant STAT3 expression and activity, not only on tumor cells, but in elements of the TME and circulating leukocytes. STAT3 is a transcription factor that can be activated by cytokines and growth factors. This project works with the hypothesis that molecules and extracellular vesicles secreted by cells in the TME can have local and systemic effects on STAT3 activation, and that STAT3 inhibition may promote anti-tumor immune responses in these types of cancer (image bellow), therefore collaborating with other therapy protocols. Using multiparametric flow cytometry and proteomics, we will characterize mechanisms of STAT3 activation, STAT3 role in immunomodulatory mechanisms and finally, the effects of its inhibition on tumor cells and leukocytes. We will focus on cervical and ovarian cancers, both representing an important burden for women's health. (AU)