5-Fluorouracil Effectively Depletes Tumor Induced Myeloid Derived Suppressor Cells in 4T1 Mammary Carcinoma Model

Abstract

Background: Myeloid Derived Suppressor Cells (MDSCs) are capable of inhibiting both innate and adaptive immune responses and accumulate in the microenvironment of breast tumors. Hence, MDSC depletion by chemotherapeutic agents can improve clinical efficacy of cancer immunotherapy. The effects of 5-FU and doxorubicin agents on MDSC reduction in 4T1 breast cancer murine model were evaluated. Methods: 5×105 of 4T1 tumor cells were injected into mammary fat pad of BALB/c female mice. Tumor bearing mice were randomly divided into 4 groups: PBS receiving control group, doxorubicin receiving groups at doses of 2.5 and 5 mg/kg, and 5-FU receiving group at dose of 50 mg/kg. Doxorubicin and 5-FU agents were intraperitoneally administrated at three doses with 5-day intervals and five doses for three times a week, respectively. Then, on day 20 post tumor cells injection, spleens and tumors were isolated to determine frequency of CD11b+ Gr1+ MDSCs by flow cytometry analysis. Results: 5-FU was able to reduce significantly both splenic and interatumoral MDSCs comparing to control group (p=0.0276 and p=0.0067, respectively). Also, Doxorubicin treatment at dose of 50 mg/kg was associated to a significant reduction of splenic MDSCs in comparison to untreated group (p=0.0382). However, only 5-FU injection led to inhibit notably tumor growth in comparison to control group (p=0.0139). Conclusion: Findings show that 5-FU has inhibitory effects on MDSCs and tumor growth in 4T1 tumor model. So, more investigations are needed to study combination of 5-FU with immune based approaches to enhance the efficacy of cancer therapies.