Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells

• Autor(a) principal: Camargo, Marcela Rodrigues de [UNESP]
• Data de Publicação: 2017
• Outros Autores: Gorgulho, Carolina Mendonca [UNESP], Rodrigues, Cecilia Pessoa [UNESP], Penitenti, Marcimara, Longo Frederico, Juliana Cristina [UNESP], Marchesan Rodrigues, Maria Aparecida [UNESP], Kaneno, Ramon [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1089/cbr.2017.2259; http://hdl.handle.net/11449/163407
• topic: chemotherapy; colorectal cancer; dendritic cell; immunomodulation; vaccine

Aim: Considering the central role of dendritic cells (DCs) on the development of an antitumor immune response, in this study we used a murine model to evaluate how DC transfection with drug-treated tumor cell RNA changes their phenotype, and whether transfection enhances the in vivo effectiveness of a DC-based antitumor vaccine. Materials and Methods: MC-38 colorectal tumor cells were pretreated with the minimum effective concentration of 5-fluorouracil (5-FU), then their total RNA was extracted and transfected into DCs. These DCs were inoculated into C57Bl/6 mice bearing subcutaneous MC-38 tumor. Results: DC transfection with drug-treated tumor RNA increases the percentages of CD40(+) (from 37.6% to 61.4%), CD86(+) (from 39.8% to 53.4%), and major histocompatibility complex class II+ (from 51.2% to 75.3%) cells, whereas significantly increases the in vivo generation of interferon-c producer lymphocytes. Conclusion: These results reinforce our view that treatment of tumor cells with 5-FU induces transcriptional changes that can be transferred to DCs by RNA transfection, enhancing their ability to stimulate an antitumor response.