Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets

Autor(es)

Romagnoli, Graziela Gorete ^[1] ; Zelante, Bruna Barbosa ^[1] ; Toniolo, Patricia Argenta ^[1] ; Migliori, Isabella Katz ^[1] ; Barbuto, Jose Alexandre M. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Ctr Cellular & Mol Studies & Therapy NETCEM, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 5, JAN 19 2015.
• Citações Web of Science: 41

Resumo

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-gamma-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. (AU)

• Processo FAPESP: 04/09956-0 - Modulação funcional de células dentríticas em diferentes situações fisiopatológicas
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/58597-1 - Exossomos derivados de celulas dendriticas como adjuvantes naturais na resposta antitumoral.
• Beneficiário: Graziela Gorete Romagnoli
• Modalidade de apoio: Bolsas no Brasil - Doutorado