Estudo do microambiente tumoral em carcinoma epidermoide oral e orofaríngeo e sua implicação prognóstica

Abstract

Inflammatory cells can assist important processes of carcinogenesis, such as angiogenesis, invasion and metastasis. It has been shown that systemic inflammation, as well as the presence of tumour-infiltrating inflammation cells, negatively affects the clinical outcome. In this sense, the prognostic value of inflammatory markers has been explored in several types of cancer. In this study, we investigated the potential biomarker of the pre-treatment neutrophil-lymphocyte ratio (NLR) in peripheral blood, PD-L1 expression in tumour and inflammatory cells and tumour-associated neutrophils and lymphocytes in oral and oropharyngeal squamous cell carcinoma (OSCC). An international multicenter retrospective study was conducted with biological samples, clinical and follow-up data from 199 individuals with OSCC from Brazil and United Kingdom. Histological slides were evaluated for invasion pattern, Tumour-infiltrating lymphocytes (TIL) and presence of vascular, lymphatic and perineural invasion. Paraffinized tumour tissues were subjected to immunohistochemical reaction to identify tumour-associated neutrophils (TAN) and to evaluate PD-L1 expression. To determine NLR, absolute neutrophil and lymphocyte counts were obtained from blood counts performed in the period prior to treatment. TAN and NLR were dichotomized according to the cutoff, established by means of a ROC curve. TIL was classified as low, moderate and high and the PD-L1 expression was assessed using the Combined Positive Score (CPS) method. Our results showed that peritumoral neutrophils were associated with worse disease-free survival. Low TIL and increased NLR were associated with larger tumor size and advanced disease. Increased NLR was also associated with smoking and drinking. PD-L1 expression did not show a significant association with the clinical-pathological characteristics and prognostic indicators analysed. The inflamed tumor microenvironment, characterized by the high expression of PD-L1, low TIL and high TAN, was associated with worse overall survival. Our investigations indicate that systemic inflammation and the inflamed tumour microenvironment can be considered as prognostic biomarkers in OSCC, however, in our sample group, the increase in NRL was not related to the increase in neutrophil infiltration and the inflamed tumor microenvironment.