multiple low doses of 5-fluorouracil diminishes immunosuppression by myeloid derived suppressor cells in murine melanoma model
نویسندگان
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.
منابع مشابه
Multiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model
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 ...
متن کاملRPN13/ADRM1 inhibitor reverses immunosuppression by myeloid-derived suppressor cells
Myeloid-derived-suppressor cells (MDSCs) are key mediators of immune suppression in the ovarian tumor microenvironment. Modulation of MDSC function to relieve immunosuppression may enhance the immunologic clearance of tumors. The bis-benzylidine piperidone RA190 binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory particle of the proteasome and directly kills ovarian cancer cells b...
متن کاملDifferentiation of Murine Myeloid-Derived Suppressor Cells
Myeloid-derived suppressor cells (MDSCs) are frequently defined as a heterogeneous population of immature cells belonging to the myeloid lineage which possess strong immunosuppressive activities. These cells ultimately derive from myeloid progenitors mainly present in the bone marrow that undergo a dysregulated differentiation pathway, ending up with the systemic mobilization of MDSCs of “monoc...
متن کاملTargeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression
The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits antitumor immune responses, supporting the dis...
متن کاملRegulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer
Background: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. Objective: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease...
متن کاملMonocytic myeloid-derived suppressor cells in advanced melanoma patients
The percentage of circulating CD14+CD11b+HLA-DR-/low myeloid-derived suppressor cells (MDSCs) inversely correlates with survival among advanced melanoma patients. High levels of MDSCs are associated with the absence of T lymphocytes specific for melanoma-derived antigens, implying a causal and clinically relevant interaction between these cell subsets. MDSCs might therefore represent prognostic...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
iranian journal of immunologyجلد ۱۲، شماره ۳، صفحات ۱۷۶-۱۸۷
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023