Expressão de biomarcadores proteicos do sistema imune (CD4 e CD8) em carcinomas epidermoides de boca

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. The tumor microenvironment (TME) is made up of components from both the tumor and the host. The immune cells of the TME, mainly CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs), as well as others, suppress the proliferation of malignant cells and play a crucial role in the progression of CEB. This study aims to characterize the protein expression of CD4+ and CD8+ immune cells as well as the amount of TILs in the CEB microenvironment and their relationship with clinicopathological parameters and patient survival. This is an observational, cross-sectional study, based on evaluations of samples mainly from biopsies, but also surgical specimens and cases diagnosed as CEB between January 2014 and December 2018, from a pathology laboratory in Manaus/AM. To this end, the samples were subjected to histopathological analysis including classification, degree of keratinization, arrangement of cellular arrangements, TILs and items from the College of American Pathologists (the latter for surgical specimens). All the samples were then subjected to immunohistochemistry with antibodies against CD4 and CD8 lymphocytes. For statistical analysis, Pearson's chi-square test was used to verify associations between the variables analyzed, as well as the relationship between TIL density and inflammatory infiltrate. Kaplan-Meier curves were used to characterize survival, and the Kruskal-Wallis ANOVA test was used to associate clinicopathological variables with survival. A significance level of 5% was considered for all tests. A total of 20 samples were included, 75% (15) of which were well-differentiated CEBs with 75% (15) of the cases containing high TIls (between 41% and 90%) in a context of intense inflammatory infiltrate (50% of the cases). A positive correlation was observed between TILs and inflammatory infiltrate (p=0.027). All the cases had a low frequency of CD4+ lymphocytes, while half the cases had a low frequency of CD8+ lymphocytes and the other half a high frequency of this marker, i.e. 50% of the cases had a CD4low/CD8low profile and 50% a CD4low/CD8high profile, and 53% of the well-differentiated cases had high levels of CD8. There was no association between clinicopathological characteristics and survival time. The results of the study illustrate that the samples present classic clinicopathological characteristics of conventional well-differentiated CEB containing intense infiltrate and high TILs. There was no association between the CD4 and CD8 biomarkers and the proposed clinicopathological parameters or survival. However, there was a high frequency of CD8 lymphocytes in malignant CEB cells, especially in well-differentiated cases, which indicates their cytotoxic role against tumor cells with more favorable histological characteristics, although they also had this profile in the majority of samples with recurrence. The more prominent participation of the CD8 T lymphocyte compared to the CD4 T lymphocyte as an inflammatory element in the context of Hallmark cancer is suggested. More studies are needed to establish the exact relationship of these markers with clinicopathological parameters and with the survival of patients affected by CEB.