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Master's Dissertation
DOI
https://doi.org/10.11606/D.10.2019.tde-02072019-114551
Document
Author
Full name
Cássia Corrêa Yasumaru
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Gomes, Cristina de Oliveira Massoco Salles (President)
Nishiya, Adriana Tomoko
Xavier, José Guilherme
Title in Portuguese
Avaliação do crosstalk entre os Linfócitos Infiltrantes de Tumor (TILs) e o Fator Regulador de Interferon 8 (IRF-8) no Microambiente Tumoral: estudo em melanoma oral canino
Keywords in Portuguese
Canino
IRF-8
Linfócitos
Melanoma oral
TILs
Abstract in Portuguese
As células imunes interagem com os tumores sólidos infiltrando ativamente estas neoplasias e liberando fatores solúveis que irão influenciar na progressão tumoral. Dentre as células imunes que participam e interferem neste imunoambiente estão os TILs, Linfócitos Infiltrantes de Tumor, cuja presença pode ser benéfica ou prejudicial ao paciente, dependendo do seu subtipo e citocinas produzidas. O interferon gama, uma citocina produzida por linfócitos T, induz a expressão de IRF-8 (Fator Regulatório de Interferon 8) nas células tumorais. Estudos baseados em células humanas e murinas revelaram que este fator de transcrição, entre outras ações biológicas, está envolvido na sensibilização das células tumorais à apoptose. O objetivo deste estudo foi avaliar qualitativamente e quantitativamente o infiltrado linfocitário e a expressão do IRF8 no melanoma oral canino. Para tal, foi realizado um estudo prospectivo com 50 amostras de melanoma canino, nas quais foram avaliados o infiltrado linfocitário por meio da análise histopatológica e a imunofenotipagem por citometria de fluxo. A expressão de IRF-8 nas células tumorais foi avaliada pelo método de imuno-histoquímica. De modo geral, este estudo indicou que nos melanomas orais caninos o infiltrado linfocitário intratumoral abundante e de padrão de distribuição difuso, composto principalmente por células T CD8+, foi associado aos tumores de fenótipos menos agressivos e a uma sobrevida maior. A imunomarcação do IRF-8 foi mais pronunciada nas células tumorais dos melanomas que possuíam uma quantidade alta de TILs, mas a expressão deste fator não alterou a sobrevida dos pacientes. Portanto, os resultados deste trabalho sugerem que a análise do infiltrado linfocitário no melanoma canino pode auxiliar na caracterização do comportamento tumoral.
Title in English
Evaluation of Crosstalk between Tumor Infiltrating Lymphocytes (TILs) and Interferon 8 Regulatory Factor (IRF-8) in the Tumor Microenvironment: a study of canine oral melanoma
Keywords in English
Canine
IRF-8
Lymphocytes
Oral Melanoma
TILs
Abstract in English
Immune cells interact with solid tumors by actively infiltrating these neoplasms and releasing soluble factors that will influence tumor progression. Among the immune cells that participate and interfere in this immunoenvironment are TILs, Tumor Infiltrating Lymphocytes, whose presence may be beneficial or harmful to the patient, depending on their subtype and produced cytokines. Interferon gamma, a cytokine produced by T lymphocytes, induces the expression of IRF-8 (Regulatory Factor of Interferon 8) in tumor cells. Studies based on human and murine cells have revealed that this transcription factor is involved in the sensitization of tumor cells to apoptosis, among other biological actions. The objective of this study was to evaluate qualitatively and quantitatively the lymphocytic infiltrate and the expression of IRF8 in oral canine melanoma. A prospective study was carried out with 50 samples of canine melanoma, in which the lymphocytic infiltrate was evaluated by histopathological analysis and immunophenotyping by flow cytometry. Expression of IRF-8 in tumor cells was assessed by the immunohistochemistry method. In general, this study indicated that an abundant intratumoral lymphocytic infiltrate and diffuse distribution pattern, composed mainly of CD8+ T cells, was associated with less aggressive tumor phenotypes and with a longer survival in the canine oral melanomas. Immunoblotting of IRF-8 was more pronounced in melanoma tumors that had a high amount of TILs, but expression of this factor did not alter patient survival. Therefore, the results of this work suggest that the analysis of the lymphocytic infiltrate in canine melanoma can help in the characterization of the tumor behavior.
 
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Publishing Date
2019-10-14
 
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