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Effect of the tumor microenvironment on the function and phenotype of dendritic cells generated in vitro from monocytes obtained from healthy volunteers and breast cancer patients.

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Author(s):
Ana Paula Silva de Azevedo dos Santos
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Jose Alexandre Marzagao Barbuto; Cristina Bonorino; Niels Olsen Saraiva Câmara; Fábio Martins Laginha; Elaine Guadelupe Rodrigues
Advisor: Jose Alexandre Marzagao Barbuto
Abstract

In breast cancer, the tumor metabolism, the action of estrogens antagonists can influence dendritic cells (DC) generation. The aim of this work was to evaluate the frequency of DCs in tumor tissue and the differentiation of DCs derived from peripheral blood mononuclear cells (PBMCs) and compared the phenotypic and functionally of these cells from healthy individuals and breast cancer patients. The results showed that patients PBMCs were unable to generate phenotypicaly, functionally mature DCs and presented larger production of interleukin 10 and higher expression of HSP27 when compared with healthy volunteers\' DCs, presented higher production of Interferon-gamma. The p38 MAPK signaling pathway seems to be important in PBMCs differentiation into DCs, and its activation by stress can induce the synthesis of HSP27, that inhibits DC generation. The tamoxifen treatment caused modulation of membrane DC markers expression. Therefore, these results show that patients\' DCs present phenotypic and functional alterations which can be caused by tumor microenvironment. (AU)