Multiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model Pubmed



Namdar A¹ ; Mirzaei HR² ; Jadidiniaragh F³ ; Ashourpour M³ ; Ajami M⁴ ; Hadjati J² ; Rezaei A¹
Source: Iranian Journal of Immunology Published:2015

Abstract

Background: Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression. Objective: To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model. Methods: Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8 + T cells as well as tumor growth and survival were evaluated in drug treated and untreated mice. Results: Our results demonstrated that this therapeutic strategy increases the overall mice survival (p≤0.01) and induces melanoma-specific CD8 + T cell immunity (p≤0.01) by reducing the frequency of myeloid derived suppressor cells (p≤0.01) as well as their immune suppressive functions (p≤0.05). Conclusion: Altogether, our data suggest that 5-fluorouracil in multiple low regimens might be used to overcome tumor immunosuppression and improve the efficacy and outcome of antitumor immune responses in a mouse model. © 2015, Shiraz University of Medical Sciences. All rights reserved.