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01-03-2018 | Original Article

Prophylactic DNA vaccine targeting Foxp3⁺ regulatory T cells depletes myeloid-derived suppressor cells and improves anti-melanoma immune responses in a murine model

Authors: Afshin Namdar, Reza Mirzaei, Arash Memarnejadian, Roobina Boghosian, Morteza Samadi, Hamid Reza Mirzaei, Hamid Farajifard, Mehdi Zavar, Kayhan Azadmanesh, Shokrollah Elahi, Farshid Noorbakhsh, Abbas Rezaei, Jamshid Hadjati

Published in: Cancer Immunology, Immunotherapy | Issue 3/2018

Abstract

Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model. Our results indicate that Foxp3 vaccination continuously reduces Treg population in both the tumor site and the spleen. Surprisingly, Treg reduction was associated with a significant decrease in the frequency of MDSC, both in the spleen and in the tumor environment. Furthermore, Foxp3 vaccination resulted in a significant reduction of arginase-1(Arg-1)-induced nitric oxide synthase (iNOS), reactive oxygen species (ROS) and suppressed MDSC activity. Moreover, this concurrent depletion restored production of inflammatory cytokine IFN-γ and enhanced tumor-specific CTL response, which subsequently resulted in the reduction of tumor growth and the improved survival rate of vaccinated mice. In conclusion, our results revealed that Foxp3 vaccine promotes an immune response against tumor by targeting both Treg and MDSC, which could be exploited as a potential immunotherapy approach.

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Title: Prophylactic DNA vaccine targeting Foxp3+ regulatory T cells depletes myeloid-derived suppressor cells and improves anti-melanoma immune responses in a murine model
Authors: Afshin Namdar
Reza Mirzaei
Arash Memarnejadian
Roobina Boghosian
Morteza Samadi
Hamid Reza Mirzaei
Hamid Farajifard
Mehdi Zavar
Kayhan Azadmanesh
Shokrollah Elahi
Farshid Noorbakhsh
Abbas Rezaei
Jamshid Hadjati
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 3/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2088-6

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