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Doctoral Thesis
DOI
10.11606/T.42.2017.tde-14032017-100604
Document
Author
Full name
Simone Cardozo Stone
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Lepique, Ana Paula (President)
Andrade, Luciana Nogueira de Sousa
Bargieri, Bruna Cunha de Alencar
Freitas, Vanessa Morais
Vessoni, Sandra Coccuzzo Sampaio
Title in Portuguese
Papel do metabolismo de tumores associados ao papilomavírus humano na modulação do fenótipo de macrófagos humanos.
Keywords in Portuguese
Câncer cervical
Imunomodulação
Lactato
Macrófagos
Papilomavírus humano
Abstract in Portuguese
O lactato, produto do metabolismo alterado das células tumorais, possui papel na modulação de fenótipo supressor em células imunes. Macrófagos são uma das principais células do microambiente tumoral, sendo pró-tumorais em câncer cervical. O objetivo desse trabalho foi avaliar o efeito do lactato no fenótipo de macrófagos associados a células tumorais derivadas de câncer cervical. Linhagens celulares positivas e negativa para HPV foram utilizadas para formação de esferoides tumorais, os quais receberam monócitos de doadores saudáveis para diferenciação em macrófagos. Macrófagos cultivados com linhagens tumorais positivas para HPV apresentaram fenótipo misto e pró-tumoral, enquanto os cultivados com a linhagem negativa, um fenótipo mais anti-tumoral. A inibição da enzima lactato desidrogenase, nas células tumorais, promoveu diferentes efeitos no fenótipo dos macrófagos, dependendo do tipo celular a que estavam associados. Essas alterações diminuíram o aspecto pró-tumoral desses macrófagos, que induziram maior proliferação de linfócitos T e morte de células tumorais.
Title in English
The role of HPV-associated tumor metabolism on human macrophage phenotype.
Keywords in English
Cervical cancer
Human papilomavirus
Immumodulation
Lactate
Macrophage
Abstract in English
The lactate, product of the altered metabolism of tumor cells, is associated with the induction of a suppressor phenotype in immune cells. Macrophages are one of the major cells of the tumor microenvironment, and are pro-tumor in cervical cancer. The aim of this study was to evaluate the effect of lactate in the phenotype of macrophages associated with tumor cells derived from cervical cancer. HPV positive and negative cell lines were used for formation of tumor spheroids, which received healthy donor monocytes to differentiate into macrophages. Macrophages cultivated with HPV positive tumor cell lines presented a mixed and pro-tumor phenotype, while macrophages cultivated with the HPV negative cell line, a more anti-tumor phenotype. Inhibition of lactate dehydrogenase in the tumor cells promoted different effects on macrophages phenotype, depending on the cell type that they were associated. These changes decreased the pro-tumor property of macrophages, which were able to induced T cell proliferation and tumor cell death.
 
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Release Date
2019-03-14
Publishing Date
2017-03-14
 
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