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

Abstract

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-γ 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.