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

Cancer Biother Radiopharm. 2017 Oct;32(8):302-308. doi: 10.1089/cbr.2017.2259.

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.

Keywords: chemotherapy; colorectal cancer; dendritic cell; immunomodulation; vaccine.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / therapy*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Fluorouracil / administration & dosage*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • RNA, Neoplasm / genetics*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transcription, Genetic / drug effects
  • Transfection / methods
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Antimetabolites, Antineoplastic
  • Cancer Vaccines
  • RNA, Neoplasm
  • Fluorouracil