Suppressive bias of dendritic cells in cancer: investigation in human and murine model possible mechanisms

Abstract

Dendritic cells (DCs) are the main antigen-presenting cells and several studies have shown that the phenotypic and functional state of these cells may reflect the nature of immune responses against different stimuli. The possibility of DCs generation from blood monocytes in vitro allowed large gain in knowledge about these cells and, also, the development of immunotherapy protocols, especially in cancer patients. Nevertheless, the use of monocytes-derived DCs from cancer patients appears to be a defective tool for use in immunotherapy trials. Our group in Brazil has demonstrated that monocytes-derived DCs from cancer patients reveal a bias towards the induction of regulatory T lymphocytes. Moreover, the French group studying intratumoral DCs, describes the ability of those cells in attract T lymphocytes with suppressive profile to the tumor microenvironment. Therefore, our first objective is to evaluate the ability of patients' DCs (from blood and intratumoral) to, actually, stimulate patients' regulatory T lymphocytes. At the same time, we intent to evaluate the hypothesis that the deviations of DCs capability and their precursors are dependent on soluble factors produced in the tumor microenvironment. Finally, to investigate a second hypothesis, that the DCs deviation depend on hematopoietic alteration, we will use a murine model of mammary carcinoma (transgenic MMTV/neu) to evaluate, in vivo, DCs differentiation from bone marrow precursors. (AU)