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

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Camargo, Marcela Rodrigues de [UNESP]
Gorgulho, Carolina Mendonca [UNESP]
Rodrigues, Cecilia Pessoa [UNESP]
Penitenti, Marcimara
Longo Frederico, Juliana Cristina [UNESP]
Marchesan Rodrigues, Maria Aparecida [UNESP]
Kaneno, Ramon [UNESP]

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Mary Ann Liebert, Inc


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.



chemotherapy, colorectal cancer, dendritic cell, immunomodulation, vaccine

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Cancer Biotherapy And Radiopharmaceuticals. New Rochelle: Mary Ann Liebert, Inc, v. 32, n. 8, p. 302-308, 2017.