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Multiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model | ||
Iranian Journal of Immunology | ||
مقاله 3، دوره 12، شماره 3، آذر 2015، صفحه 176-187 اصل مقاله (1.87 M) | ||
نوع مقاله: Original Article | ||
نویسندگان | ||
Afshin Namdar1؛ Hamid Reza Mirzaei2؛ Farhad Jadidi-Niaragh3؛ Mahboubeh Ashourpour3؛ Maryam Ajami4؛ Jamshid Hadjati2؛ Abbas Rezaei* 1 | ||
1Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan | ||
2Department of Immunology, School of Medicine | ||
3Department of Pathobiology, School of Public Health | ||
4Department of Immunology, School of Medicine, Tarbiat Modares University, Tehran, Iran | ||
چکیده | ||
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 cellsmediated 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. | ||
کلیدواژهها | ||
5-Fluorouracil؛ Melanoma؛ Myeloid Derived Suppressor Cells | ||
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