Document Type : Original Article
Authors
- Afshin Namdar 1
- Hamid Reza Mirzaei 2
- Farhad Jadidi-Niaragh 3
- Mahboubeh Ashourpour 3
- Maryam Ajami 4
- Jamshid Hadjati 2
- Abbas Rezaei 1
1 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
2 Department of Immunology, School of Medicine
3 Department of Pathobiology, School of Public Health
4 Department of Immunology, School of Medicine, Tarbiat Modares University, Tehran, Iran
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 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.
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