Immune cell infiltration and HLA class I molecules in a preclinical mouse model of aggressive thyroid cancer undergoing combination therapy

• Grant number: 18/16189-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 14, 2019
• End date: January 13, 2020
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Eduardo Antônio Donadi
• Grantee: Bruna Cristina Bertol
• Supervisor: Jena D. French Baertschi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Colorado, Denver (CU), United States
• Associated to the scholarship: 15/26556-0 - Association of HLA-G, BRAF and TERT genes with malignancy of papillary thyroid carcinoma, BP.DR

Abstract

Differentiated thyroid carcinomas (DTC), which include papillary thyroid carcinoma (PTC), may present an aggressive behavior in some patients or even progress to undifferentiated anaplastic thyroid carcinoma (ATC), whose prognosis is very poor. Such patients could benefit from additional immune-based therapies. Dr. French previous studies have revealed a suppression (FoxP3+ regulatory T cells) and dysfunctional (PD-1+ T cells) status of immune response in human metastatic PTC. It is also known that human PTC tissue express the inhibitory checkpoint human leukocyte antigen (HLA)-G and -E molecules, and our ongoing studies have also investigated different aspects about the role of HLA-G molecule and HLA-G gene in PTC patients. However, more studies are needed to explore the host immune response in thyroid tumor development and in the response to therapeutic strategies. Thus, we aim to work with a preclinical aggressive DTC mouse model, available in a laboratory specialized in the study of the immune response in thyroid cancer, coordinated by Dr. French. In this context, we aim to characterize the immune infiltrate and MHC class I molecules expression throughout tumor progression, before and after treatment with different therapy approaches. This proposal agrees with our ongoing studies in Brazil and will greatly contribute to better understand the relationship between immune system and thyroid tumorigenesis, as well as the evaluation of potential new therapeutic targets to treat aggressive forms of thyroid cancer. (AU)