The role of STING in trained innate immunity to improve cancer immunotherapy.

• Grant number: 24/19233-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Sergio Costa Oliveira
• Principal researcher abroad: Glen Barber
• Institution abroad: Ohio State University, United States
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/02577-5 - Study of the mechanisms responsible for trained immunity induced by Bacillus Calmette-Guérin (BCG) in infectious diseases and Cancer, AP.TEM

Abstract

This project is a collaboration between Prof. Sergio Costa Oliveira from the University of São Paulo (USP) and Prof. Glen Barber from the Ohio State University (OSU). This grant will strength the already existing collaborative studies between both groups. The Barber laboratory discovered the STING (for STimulator of INterferon Genes signaling pathway). STING predominantly resides in the endoplasmic reticulum (ER) and is a sensor for cytosolic DNA triggering the production of a variety of pro-inflammatory cytokines. Direct injection of STING agonists exert potent anti-tumor effects and may even overcome checkpoint therapeutic inhibition. On the other hand, the USP group has demonstrated that immunotherapy with BCG can induce melanoma and bladder cancer tumor regression via trained immunity. Our hypothesis is that STING plays a key role in innate immunity influencing BCG-induced trained immunity and enhancing cancer immunotherapy. To test this hypothesis, we will investigate the following aims: (i) to test the efficacy of STING-dependent Adjuvants or Activators (STAVs) together with BCG in tumor regression and (ii) to evaluate whether the strategy of STING-dependent Adjuvants or Activators (STAVs) together with BCG enhances trained innate immunity. This grant will allow mobility between both groups and will impact at educational and research levels in both institutions. (AU)