Low Noncytotoxic Concentrations of 5-Fluorouracil Have No Adverse Effects on Maturation and Function of Bone Marrow-Derived Dendritic Cells in vitro: A Potentially Safe Adjuvant for Dendritic Cell-Based Cancer Therapy

Int Arch Allergy Immunol. 2015;168(2):122-30. doi: 10.1159/000442290. Epub 2015 Dec 18.

Abstract

Background: Low, noncytotoxic concentrations of various chemotherapeutic drugs like 5-fluorouracil (5-FU) induce antitumor immune responses by selectively depleting tumor-induced immunosuppressive cells, and could therefore be used in combination with dendritic cell (DC) vaccines in order to enhance their immunotherapeutic efficacy. However, the likely negative influences of low, noncytotoxic doses of 5-FU on bone marrow-derived (BM)-DCs in vitro have not yet been investigated.

Methods: The effects of low, noncytotoxic concentrations of 5-FU on mouse BM-DC differentiation and maturation markers (CD11c, MHC class II and CD80) as well as antigen-presenting capacity and cytokine production (IL-12p70 and IL-10) have been assessed.

Results: Different low doses of 5-FU had no significant effect on the expression of DC differentiation and maturation or on costimulatory markers (p = 0.5). Furthermore, suboptimal doses of 5-FU did not affect the immunostimulatory functions of DCs such as antigen presentation (p = 0.6) and cytokine production (p = 0.9).

Conclusions: These data suggest that low doses of 5-FU have no adverse effects on DC maturation and function, and the efficacy of DC-based cancer immunotherapy may be greatly enhanced by combining it with suboptimal doses of 5-FU.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Bone Marrow Cells / cytology
  • Cancer Vaccines
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Female
  • Fluorouracil / pharmacology*
  • Interleukin-10 / immunology
  • Interleukin-12 / immunology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / therapy

Substances

  • Adjuvants, Immunologic
  • Antimetabolites, Antineoplastic
  • Cancer Vaccines
  • IL10 protein, mouse
  • Interleukin-10
  • Interleukin-12
  • Fluorouracil