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" Investigation of the Targeting of Regulatory T Cells and Myeloid Derived Suppressor Cells on the Efficacy of DC Vaccine Immunotherapy in Experimental Model of Melanoma "
/Afshin Namdar
; Abbas Rezaei, Jamshid Hadijati, Farshid Noorbakhsh, Mohammad Reza Maracy
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Isfahan University of Medical Sciences
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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104714
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| Doc. No
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T15544
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| Call number
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QW568,N174i,2015
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| Main Entry
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Namdar, Afshin
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| Title & Author
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Investigation of the Targeting of Regulatory T Cells and Myeloid Derived Suppressor Cells on the Efficacy of DC Vaccine Immunotherapy in Experimental Model of Melanoma/Afshin Namdar
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| College
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Schools, Medical
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| Date
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, 2015
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| Degree
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Immunology, Ph.D
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| Page No
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xii, 89 p.: ill, tab
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| Note
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This is a research dissertation with project ID 391146
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افشین نامدار
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| Abstract
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Despite dendritic cell (DC)-based cancer vaccine is recognized as one of the powerful active immunotherapy to launch effective adaptive immunity against tumors, immune suppressions mediated by tumor microenvironment limit dendritic cells to induce efficient anti-tumor responses. Among these suppressive mechanisms, regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC) are predominant. They both play crucial role in maintaining a suppressive environment and inhibiting anti-tumor T cell responses. Therefore, targeting Treg and MDSC could be an alternative approach that might overcome the immune suppression in tumor microenvironment and improve DC vaccine efficacy. In the present study, a novel combination therapy comprised of Foxp3 DNA/recombinant protein vaccine and multiple low non-cytotoxic concentration of 5-fluorouracil was designed against Tregs and MDSCs, respectively, in order to dampen the immune suppression and increase DC vaccine efficacy in favor of anti-tumor CTL activity. The results demonstrated that this novel combination therapy increased mice survival and abrogated tumor growth significantly in comparison with control groups, which is due to marked reduction of MDSCs and Tregs frequency and suppressive functions. This reduction was also accompanied with significant improvement of DC vaccine efficacy by inducing the potential CTL responses. Taken together, these findings suggest that controlling immunosuppressive cells during tumor progression could enhance DC vaccine activity and thus support anti-tumor immunity.
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| Descriptor
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Dendritic Cells
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Suppressor Factors, Immunologic
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Melanoma
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Leukemia, Myeloid
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Cancer Vaccines
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| Added Entry
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Rezaei , Abbas, Thesis advisor
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Hadjati, Jamshid, Thesis advisor
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Noorbakhsh, Farshid, Thesis advisor
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Maracy, Mohammad Reza, Thesis advisor
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| Translated Title Supplied by Cataloguer
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بررسی تاثیر حذف همزمان سلول های Treg و MDSC در افزایش کارایی ایمونوتراپی در مدل تجربی ملانوما
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