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

Namdar, A. and Mirzaei, R. and Memarnejadian, A. and Boghosian, R. and Samadi, M. and Mirzaei, H.R. and Farajifard, H. and Zavar, M. and Azadmanesh, K. and Elahi, S. and Noorbakhsh, F. and Rezaei, A. and Hadjati, J. (2018) Prophylactic DNA vaccine targeting Foxp3+regulatory T cells depletes myeloid-derived suppressor cells and improves anti-melanoma immune responses in a murine model. Cancer Immunology, Immunotherapy, 67 (3). pp. 367-379.

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Abstract

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. Keywords Regulatory T cells Myeloid-derived suppressor cells Foxp3 Melanoma

Item Type: Article
Additional Information: cited By 0
Subjects: Immunology and Microbiology
Divisions: Faculty of Medicine > Basic Sciences > Department of Microbiology & Immunology
Depositing User: ART . editor
Date Deposited: 09 Apr 2019 07:43
Last Modified: 09 Apr 2019 07:43
URI: http://eprints.kaums.ac.ir/id/eprint/3208

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