Role of immune response control molecules/genes (checkpoint) in the pathogeny and treatment of Clear Renal Cell Carcinoma

• Grant number: 23/00238-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2023
• Status: Discontinued
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Antônio Donadi
• Grantee: Rafaela Miranda Barbosa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The human leukocyte antigen G (HLA-G) is a promiscuous immune checkpoint molecule, inhibiting different costimulatory pathways, interfering with the functionality of different cells of the immune system, being associated with the emergence and progression of several diseases, including cancer. Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of RCC in the world, with high morbidity and mortality. The use of immunotherapy that inhibit immune checkpoints - such as the combination of Nivolumab (anti-PD-1) and Ipilimumab (anti-CTLA-4) - has shown promising results for advanced ccRCC. However, a considerable number of patients do not respond satisfactorily to this treatment. Several studies have reported that increased tissue expression of HLA-G and elevated levels of soluble HLA-G in the plasma of patients with ccRCC are associated with a worse prognosis. This study aims to broaden the understanding of the role of molecules that act in the control of the immune response (specific/promiscuous) in the pathogenesis and treatment of ccRCC, through the characterization of genetic, transcriptional, pos- transcriptional and protein factors, correlating them with the different responses to treatment with Nivolumab and Ipilimumab. It is expected to identify factors associated with the modulation of immune checkpoint genes and propose parameters to identify patients prone to have a better response to the combined therapy with Nivolumab and Ipilimumab, i.e., those who express less HLA-G. (AU)