The immunological microenvironment of thyroid cancer and its clinical application: A comprehensive approach.

• Grant number: 24/06697-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lucas Leite Cunha
• Grantee: Lucas Leite Cunha
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Carlos Lenz Cesar ; Fernando Augusto Soares ; Janete Maria Cerutti ; Laura Sterian ; Niels Olsen Saraiva Câmara ; Rodrigo de Andrade Natal ; Rodrigo Nalio Ramos ; Rui Monteiro de Barros Maciel ; Soraya Soubhi Smaili ; Susan Chow Lindsey

Abstract

This project aims to investigate the physiopathological mechanisms of medullary thyroid carcinoma (MTC) in patients with multiple endocrine neoplasia type 2 (MEN2). The most important and predominant clinical manifestation of patients with MEN2 is MTC. It is possible that the clinical peculiarities of MTC find molecular and immunological explanations in the peculiar composition of the immune response present in the tumor microenvironment of these patients. Therefore, our objectives are: (i) to outline the clinical profile of patients with MTC; (ii) to describe the profile of the immune response present in the tumor microenvironment of patients with MTC. This study is a translational study aimed at unraveling the mechanisms by which immune system cells interact in the composition of the tumor microenvironment of MTC. Thus, we will study a small number of patients, but each one more deeply. We will include 50 patients with MTC. Samples from these 50 patients will be obtained including fresh tissue and preserved in paraffin. We will compare our results with tissues from non-malignant lesions and normal tissues from healthy individuals. Additionally, we will compare these samples with other thyroid cancers, such as differentiated carcinoma (n=10) and poorly differentiated thyroid carcinoma (n=10). From this material, we will critically evaluate the tumor microenvironment. The investigation of the immunological profile of the microenvironment will be done using second harmonic generation techniques, immunohistochemistry, and immunofluorescence. We will complement the phenotypic evaluation of immune cells through spatial transcriptome technique. We believe this may bring new prognostic markers that assist in the individualization of clinical management of patients with MTC, as well as potentially uncover therapeutic targets in patients with MTC. (AU)