RESUMO

As células Th17 têm sido fortemente associadas à patogenia de doenças autoimunes e inflamatórias, porém sua influência na carcinogênese ainda é pouco conhecida, havendo relatos de suas ações tanto antitumorais quanto pró-tumorais. O objetivo do presente trabalho foi pesquisar a presença da linhagem Th17 intratumoral em CCE de lábio e língua, através da análise da imunoexpressão da IL-17 e do RORγt, relacionando estes achados com dados clínicos e morfológicos na tentativa de melhor compreender o papel dessas células na imunidade tumoral dos CCEOs. Na análise histomorfológica, observou-se predomínio de lesões de baixo grau em lábio e de alto grau em língua (p = 0,024). Não foi observada significância estatística entre estadiamento clínico e gradação histológica de malignidade (p = 0,644). Para o estudo imunoistoquímico, 5 campos aleatórios com maior imunorreatividade do infiltrado inflamatório peritumoral foram fotomicrografados no aumento de 400x. Realizou-se a contagem de linfócitos que exibiram marcação citoplasmática e pericitoplasmática para a citocina IL-17 bem como nuclear e citoplasmática para o RORγt. Foi observada diferença estatisticamente significativa na quantidade de linfócitos imunopositivos para IL-17 entre os grupos de CCE de lábio e língua (p = 0,028). Para o RORγt não foi observada diferença estatisticamente significativa entre os grupos de CCE de lábio e língua (p = 0,915). Não foi observada diferença estatística entre a imunomarcação da IL-17 e RORγt com gradação histológica de malignidade e com estadiamento clínico. Os achados dessa pesquisa sugerem um possível papel antitumoral da IL-17 para os casos de lábio. Os resultados da análise do RORγt, possivelmente se devem à ampla dualidade do papel pró-tumoral e antitumoral das células Th17 e à sua plasticidade que, na presença de diferentes citocinas expressas no microambiente tumoral, podem alterar seu fenótipo. (AU)

Th17 cells have been strongly associated to the pathogenesis of inflammatory and autoimmune diseases, although their influence on the carcinogenesis is still little known, there are reports of anti-tumor and protumoral actions. The objective of this study is to research the presence of Th17 lineage in lip and tongue SCC, using the analysis of the immunoexpression of IL-17 and RORγt, relating this immunoexpression with clinical and morphological findings in the attempt to better comprehend the role of these cells on the tumoral immunity of OSCCs. The results were submitted to non-parametric statistical tests with significance level of 5%. On the histomorphological analysis, it was observed the predominance of low level lesions on lip and high level lesions on tongue (p=0,024). It was not observed statistical significance between clinical stage and histological gradation of malignancy (p=0,644). For the immunohistochemical study, 5 random fields with greater immunoreactivity of the peritumoral inflammatory infiltrate were photomicrographed on the 400x magnification. It was done the count of lymphocytes which showed cytoplasmic and pericytoplasmic staining for the IL-17 cytokine as well as nuclear and cytoplasmic staining for RORγt. It was observed statistical significance difference on the quantity of immunopositive lymphocytes to IL-17 between the groups of SCC of lip and tongue (p=0,028). For the RORγt it was not observed statistical significance difference between the groups of SCC of lip and tongue (p=0,915). It was not observed statistical difference between the immunostaining of IL-17 and RORγt with histological gradation of malignancy and clinical staging. The findings of this research suggest a possible anti-tumor role of IL-17 for cases of lip. The results of the analysis of the RORγt are possibly due to the wide duality of the anti-tumor and protumoral role of the Th17 cells and their plasticity which, in the presence of different cytokines expressed on the tumor microenvironment, can alter its phenotype. (AU)

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RESUMO

It is now clear that several members of the nuclear receptor superfamily are co-expressed by macrophages, lymphocytes and other cell types that are involved in the regulation of inflammatory and immune responses. Peroxisome proliferator-activated receptors (PPAR) and nuclear liver X receptors (LXR) are members of this family known to be activated by lipid derived endogenous ligands (such as fatty acids, eicosanoids and cholesterol) and pharmacological ones. Here we review the biology of these nuclear receptors and highlight recent work that show that their activation can ameliorate inflammatory conditions, especially due to their effect on macrophage functions. The data discussed herein show the potential beneficial effect of targeting these nuclear receptors in order to improve the outcome of septic patients.

Assuntos