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Myeloid-Derived Suppressor Cells Elimination by 5-Fluorouracil Increased Dendritic Cell-Based Vaccine Function and Improved Immunity in Tumor Mice Pubmed



Khosravianfar N1 ; Hadjati J1 ; Namdar A2 ; Boghozian R1 ; Hafezi M3 ; Ashourpour M3 ; Kheshtchin N1 ; Banitalebi M4 ; Mirzaei R1 ; Razavi SA3
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Iranian Journal of Allergy# Asthma and Immunology Published:2018


Abstract

Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function. The purpose of this study was to evaluate the effect of low doses of 5-FU on the efficacy of DC-based vaccines in preventing and treating of melanoma tumor model. This research was performed on 28 melanoma tumor bearing C57BL/6 female mice. The mice were randomly divided to 4 groups, group 1 is control population while group 2 and 3 were treated with DC vaccine and 5-FU respectively and group 4 was treated with both DC Vaccine and 5-FU. The mice survival, tumor growth rate, number of MDSC and CD8+/ CD107a+ T cells in mice spleen were evaluated in each group with maximum result in group 4. Our results revealed that combination of DC vaccine and 5-FU reduced number of MDSCs (3%) and also tumor growth rate(10%)(p<0.05) and increased mice survival (70%) and increased CD8+ /CD107a+ T cells (25%). This study have shown that combinational therapy with DC vaccine improved immunity in tumor mice compared to the therapy consisting of DC vaccine or 5-FU only. © February 2018, Iran J Allergy Asthma Immunol. All rights reserved.
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