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

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. 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. 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. 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). 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 anti-tumor immune responses in a mouse model.