Treatment of colon cancer cells with 5-fluorouracil can improve the effectiveness of RNA-transfected antitumor dendritic cell vaccine

Autor(es)

De Almeida, Carolina V. ; Zamame, Jofer A. ; Romagnoli, Graziela G. ; Rodrigues, Cecilia P. ; Magalhaes, Marianna B. ; Amedei, Amedeo ; Kaneno, Ramon

• Tipo de documento: Artigo Científico
• Fonte: ONCOLOGY REPORTS; v. 38, n. 1, p. 561-568, JUL 2017.
• Citações Web of Science: 4

Resumo

Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT-116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT-116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells. The transfected DCs demonstrated an increased percentage of CD83(+), HLA-DR+, CD80(+) and CD86(+) cells. These phenotypical changes were followed by functional improvement demonstrated by the increased capacity of these DC to induce allogeneic T cell proliferation and to generate specific anti-HCT-116 cytolytic T cells, as demonstrated by IFN-gamma production following in vitro challenge with tumor cells. Our results allow us to conclude that treatment of tumor cells with a non-toxic concentration of 5-FU induces immunogenic changes that are transferred to DC by transfection of total RNA. (AU)

• Processo FAPESP: 09/18331-8 - Quimioimunomodulação com agentes antineoplásicos e geração de vacinas de células dendríticas
• Beneficiário: Ramon Kaneno
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/20494-5 - Potencial terapêutico antitumoral de células dendríticas sensibilizadas com exossomos alogênicos carregados com peptídeos prostáticos
• Beneficiário: Graziela Gorete Romagnoli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/16311-0 - Efeitos da proteína K1 de diferentes genótipos do herpesvírus associado ao sarcoma de Kaposi / Herpesvírus humano tipo 8 na expressão gênica de células endoteliais humanas in vitro
• Beneficiário: Carolina de Almeida Araujo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/18433-5 - Geração de Vacinas Antitumorais de células dendríticas humanas sensibilizadas com RNAm de células tumorais pré-tratadas com agentes antineoplásicos.
• Beneficiário: Marianna Bartelega Magalhães
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica