title: Dendritic Cell-Derived Exosomes may be a Tool for Cancer Immunotherapy by Converting Tumor Cells into Immunogenic Targets.
abstract: Dendritic cells (DCs) have been attracting attention in cancer immunotherapy because of their role in inducing and modulating effective immune responses. Besides the direct contact with other cell types and the secretion of cytokines, it is becoming clear that nanovesicles, such as exosomes (Exo), secreted by DCs also have a role in their function. Conversely, tumor-derived Exo carry antigens and have been used as a source of specific stimulus for the immune response against tumors. At the same time, several works have shown that different cells types incorporate DC-derived Exo (DC-Exo), resulting in modifications of their phenotype and function. Since DC-Exo carry many of the immune function-associated molecules of DCs, their incorporation by tumor cells could turn tumor cells into immunogenic targets. We have, therefore, treated human breast adenocarcinoma cells (SK-BR-3) with DCs-Exo and used these to stimulate previously SK-BR-3-primed CD3(+) T-cells. Sensitized T-cells cultured with DC-Exo-treated tumor cells showed a significantly higher percentage of IFN-γ-secreting cells (as measured by ELISPOT), when compared to the frequency of cells responding to non-DC-Exo-treated cells. These data show that the incorporation of DC-Exo by the tumor cells increased their ability to activate T-cells for a possibly more effective response, thus showing that DC-Exo may become another tool in cancer immunotherapy.
authors: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors: Graziela Gorete
authors: GG
authors: Romagnoli
authors: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors: Bruna Barbosa
authors: BB
authors: Zelante
authors: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors: Patrícia Argenta
authors: PA
authors: Toniolo
authors: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors: Isabella Katz
authors: IK
authors: Migliori
authors: Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil ; Center for Cellular and Molecular Studies and Therapy (NETCEM), University of São Paulo , São Paulo , Brazil.
authors: José Alexandre M
authors: JA
authors: Barbuto
keywords: cancer immunotherapy; dendritic cells; exosomes; immunomodulation; tumor cell immunogenicity; tumor immune response
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