Crosstalk bidirecional entre transição epitélio-mesenquimal e microambiente tumoral em carcinoma de células escamosas de língua oral

Abstract

Oral cancer is a significant public health issue worldwide; however, public awareness remains low, and many patients present with advanced-stage disease, contributing to its high mortality rate. This has driven the search for clinical, morphological, and molecular biomarkers that may enhance the understanding of oral carcinogenesis, although this search continues to represent an ongoing challenge for researchers in the field. In this context, the epithelial-mesenchymal transition (EMT) and components of the tumor microenvironment (TME) are highlighted as key regulators of cancer development markers, including apoptosis evasion, angiogenesis induction, dysregulation of energy metabolism, resistance to immune detection and destruction, and activation of invasion and metastasis. In this regard, this doctoral thesis aimed to investigate the current landscape of oral cancer, addressing epidemiological, histomorphological, and immunohistochemical aspects, with a focus on EMT and TME in oral squamous cell carcinoma (OSCC). The research began with an epidemiological characterization of risk factor exposure in the Brazilian context, advancing to an analysis of the practical and predictive applicability of morphological parameters, the prognostic impact of stromal cell components in the TME, the biological effects of the interaction between EMT and PD-L1 expression, and the impact of EMT on the immunosuppressive microenvironment in OSCC. The results from the studies conducted in this thesis support (1) the existence of a high-risk profile for the development of oral cancer in the Brazilian population, as a reflection of the high exposure to risk factors, (2) the use of the BD grading system and TSR/Tumor budding for predicting aggressiveness in tumors located in the oral tongue and lower lip, (3) the significant prognostic value of stromal components in the TME of OSCC, (4) the existence of a bidirectional interaction between EMT and PD-L1 expression in head and neck squamous cell carcinoma cell lines, and (5) the involvement of EMT in modulating an immunosuppressive microenvironment in oral tongue squamous cell carcinoma.