Evaluation of PD-1, TIM-3 and LAG-3 checkpoint inhibitors in 3D models of irradiated head and neck tumor cell cultures

• Grant number: 24/05090-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Lidia Maria Rebolho Batista Arantes
• Grantee: Victor Gabriel Paes
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated research grant: 19/07111-9 - Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital, AP.JP
• Associated scholarship(s): 25/03407-1 - Modelling intrahepatic cholangiocarcinoma microenvironment for drug screening, BE.EP.MS

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as an alternative treatment for patients with advanced head and neck squamous cell carcinoma (HNSCC) who do not respond to conventional treatments. Together with ICIs, radiotherapy plays an important role in activating the immune system against tumors, proving to be effective in treating these tumors. It is therefore necessary to investigate the interaction between tumor cells and lymphocytes in order to fully understand the mechanisms of inhibition and activation. OBJECTIVES: To evaluate the interaction between HNSCC cell lines and lymphocytes from the peripheral blood of healthy individuals, through a 3D co-culture model treated with immune checkpoint inhibitors and subsequently with radiotherapy, bringing the elements investigated closer to their occurrence in the clinic. MATERIALS AND METHODS: Co-culture models will be established with head and neck cell lines and CD8+ T lymphocytes. These models will be treated with anti-PD1, anti-TIM-3 and anti-LAG-3 and combinations with irradiation to evaluate the behavior and response to these treatments. For this purpose, cell viability (MTS), metabolic profile, immunophenotypic profile and immunological mediators will be evaluated by flow cytometry. EXPECTED RESULTS: We believe it will be possible to identify different response patterns for HNSCC tumors and lymphocytes with the different treatments using an in vitro testing tool, which could benefit patients sensitive to combinations of ICIs and radiotherapy in the future.