Study of extracellular vesicles in the initiation of immune response by dendritic cells and T lymphocytes

Abstract

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignant neoplasm, with high prevalence, severe morbidity, uncertain prognosis and a low five-year overall survival rate, between 40-50%. Excessive alcohol consumption is a prominent risk factor for OSCC. However, the initial stages of oral carcinogenesis guided by quiescent or non-activated fibroblasts, through the transfer of proteins in extracellular vesicles (EVs) to squamous cells and other cells in the microenvironment, is not yet known. Thus, the main objective of this project is to evaluate in a C57BL/6 animal model the role of EVs derived from fibroblasts and keratinocytes, previously treated with alcohol or not, in the modulation of immune cell response, more specifically, in the dynamics of dendritic cell communication with CD4+ and CD8+ T cells in lymph nodes. The dynamics of interaction between tissue microenvironment and lymph nodes will be evaluated using intravital two-photon excitation microscopy and laser microdissection followed by proteomics based on discovery of the primary (tongue) and lymph node (cervical and popliteal) sites. This innovative strategy will allow us to understand the immune response to the initial stimulus of malignant transformation associated with alcohol.Keywords: Oral squamous cell carcinoma; extracellular vesicles; intravital two-photon microscopy; intravital imaging; cell communication; proteomics; mass spectrometry. (AU)