The role of the STING pathway in the antitumor response during methionine restriction.

• Grant number: 24/15001-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 30, 2024
• End date: November 29, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Raquel de Souza Vieira
• Supervisor: Glen Barber
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Ohio State University, United States
• Associated to the scholarship: 21/08088-0 - The impact of short-term fasting and STING activation on metabolic-functional alterations of T lymphocytes and antitumor therapeutic efficacy, BP.DR

Abstract

Cutaneous melanoma is the leading cause of death from skin cancer worldwide and shows high resistance to radiotherapy and chemotherapy, indicating the need for alternative treatments. Tumor cells consume methionine avidly, and restricting this amino acid has been effective in hindering tumor growth in various models. Methionine is an essential amino acid involved in several metabolic pathways and biological processes. Despite its potential, the mechanisms and immunological impacts of methionine restriction on antitumor responses are not well understood.The cGAS-STING pathway is crucial for immune responses against tumors. Recent studies show that dietary methionine restriction inhibits cGAS methylation, enhancing its activation and lymphocyte recruitment to the tumor. However, due to the high cellular heterogeneity in tumors and challenges in evaluating all populations, literature on this topic is limited. Additionally, the mechanisms following cGAS activation in the context of methionine restriction remain unexplored. We believe that by employing single cell immune phenotyping and function, we can explore key immunological factors that orchestrate the antitumor action of methionine restriction.The aim of this project is to elucidate the role of STING in the antitumor response generated by methionine restriction, as well as to evaluate whether this restriction can enhance STING based immunotherapeutic approaches, such as treatment with nanoparticles containing STAVS (STING-dependent Adjuvants).