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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-18092012-104937
Document
Author
Full name
Graziela Gorete Romagnoli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Barbuto, Jose Alexandre Marzagao (President)
Lepique, Ana Paula
Oshiro, Telma Miyuki
Rios, Francisco José Oliveira
Rodrigues, Elaine Guadelupe
Title in Portuguese
Exossomos derivados de células dendríticas como adjuvantes naturais na resposta antitumoral.
Keywords in Portuguese
Células cultivadas de tumor
Células dendríticas
Células tumorais
Exossomos
Imunoterapia
Abstract in Portuguese
Exossomos (Exo) originados de células dendríticas (DCs) carregam moléculas associadas à apresentação antigênica. Neste trabalho procurou-se estabelecer se Exo de DCs seriam capazes de conferir imunogenicidade às células tumorais. Os Exo isolados de culturas de DCs expressavam as moléculas HLA-ABC, HLA-DR, CD86, CD11c, CD81, CD54 e CD18. Estes foram então adicionados às células da linhagem humana de adenocarcinoma mamário, SK-BR-3, as quais passaram a expressar as moléculas HLA-DR, CD86 e CD11c. As células tumorais modificadas pelos Exo induziram a produção de IL-6 e IL-10, detectados no sobrenadante das co-culturas destas com linfócitos T. Estas células tumorais também induziram aumento do número de linfócitos produtores de IFN-g, pré-sensibilizados contra antígenos tumorais, e aumento da expressão de SOCS3 nestes. Em conclusão, nossos resultados mostram que, Exo de DCs alteram o fenótipo de células tumorais, modificando sua interação com linfócitos T, sem induzir nas mesmas capacidade de ativar respostas proliferativas ou citotóxicas de linfócitos T in vitro.
Title in English
Dendritic cells-derived exosomes as natural adjuvants in antitumor responses.
Keywords in English
Cells cultured tumor
Dendritic cells
Exosomes
Immunotherapy
Tumor cells
Abstract in English
Exosomes (Exo) originated from dendritic cells (DCs) contain molecules involved in antigen presentation. The present work sought to determine if Exo from DCs would be able to transfer immunogenicity to tumor cells. Exo isolated from DCs cultures carried HLA-ABC, HLA-DR, CD86, CD11c, CD81, CD54 and CD18. These Exo were added to cultures of the human breast adenocarcinoma cell line, SK-BR-3, which gained expression of HLA-DR, CD86 and CD11c. Tumor cells modified by Exo induced IL-6 and IL-10 production, detected in the supernatant of their co-cultures with T lymphocytes. These tumor cells also induced an increase in the frequency of IFN-g-producing T lymphocytes, pre-sensitized against tumor antigens, and an increased expression of SOCS3. In conclusion, our results show that, Exo from DCs affect the phenotype of tumor cells, modifying their interaction with T lymphocytes, without inducing the ability to activate cytotoxic or T cell proliferative responses in vitro.
 
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Publishing Date
2012-10-23
 
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