Study of T-cell-mediated immunoediting and the mechanisms of immune evasion in proliferative verrucous leukoplakia

• Grant number: 23/04875-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2023
• End date: April 30, 2024
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Andreia Bufalino
• Grantee: Mariana Paravani Palaçon
• Supervisor: Omar Kujan
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Western Australia (UWA), Australia
• Associated to the scholarship: 22/14734-5 - Study of T cell-mediated immunoediting and immune evasion mechanisms in proliferative verrucous leukoplakia., BP.DR

Abstract

Potentially malignant oral disorders (OPMD) with epithelial dysplasia are most often associated with malignant transformation to oral squamous cell carcinoma (OSCC). Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are examples of DPMOs that share some clinical (irreversible white plaque) and microscopic (varying degrees of epithelial dysplasia) aspects, but have significantly different behavior and clinical evolution. In this context, preliminary results from our research group revealed that the high subepithelial density of CD8+ T lymphocytes and the imbalance of inflammatory cytokines probably play an important role in the pathogenesis of PVL. We also found that the increased expression of calreticulin (CRT) in PVL compared to OL, may explain the more aggressive behavior of PVL. Thus, the main hypothesis of this project considers that infiltrating CD8+ T cells in the PVL are in a state of exhaustion and that terminally "exhausted" CD8+ T cells lose CD8 receptors, suggesting the accumulation of double negative T cells in the PVL. Furthermore, the increased and persistent expression of CRT, wild or mutant, may be associated with the exhaustion process of CD8+ T cells in this OPMD. Therefore, an in-depth study of the possible mechanisms of immune evasion is necessary for a better understanding of the involvement of these processes in the pathogenesis of PVL. To test this hypothesis, we propose the following specific objectives: Evaluate the expression of T cell exhaustion markers and correlate with the expression of CRT and CD47 through immunohistochemistry in PVL samples; and evaluate the frequency and subtypes of double negative T cells in PVL, as well as their possible interrelationship with the expression of markers associated with T cell exhaustion. (AU)