Semnan University of Medical Sciences

Research and Technology Vice Chancellor

Samadi-Foroushani, Morteza and Vahabpour, Rouhollah and Memarnejadian, Arash and Namdar, Afshin and Khamisabadi, Masoumeh and Sadat, Seyed Mehdi and Asgarian-Omran, Hossein and Azadmanesh, Kayhan and Kokhaei, Parviz and Aghasadeghi, Mohammad Reza and Hadjati, Jamshid (2011) Immune responses regulation following antitumor dendritic cell-based prophylactic, concurrent, and therapeutic vaccination. Medical Oncology, 28 (S1). pp. 660-666. ISSN 1357-0560

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    Abstract

    There is ample evidence in favor of various immunosuppressive mechanisms that weaken antitumor immune responses and affect currently used immunotherapies. Induction of regulatory T cells (Treg) and secretion of indoleamine 2,3-dioxygenase (IDO) by tumor tissue are considered as two main mechanisms of tumor immune escape. However, little is known about the contribution of these mechanisms on the modulation of dendritic cell vaccine-mediated antitumor response. To address this concern, we assessed Treg's infiltration and the expression of Foxp3 and IDO genes in tumor microenvironment following dendritic cell-based antitumor immunotherapy of mice in different protocols of prophylactic, concurrent, and therapeutic vaccination. According to cytotoxicity assay, the vaccinated mice exposed efficient induction of splenic CTLs in all groups. However, only the mice immunized in prophylactic regimen significantly retarded the growth of tumor cells. Interestingly, the Treg content of tumor samples and transcriptional level of both Foxp3 and IDO genes were reduced in this group, while animals that received the vaccine in concurrent and therapeutic protocols showed increase in tumor-infiltrating Tregs and mRNA levels of Foxp3 and IDO. Accordingly, higher expression of these genes resulted in more inhibition of antitumor response. Our findings indicate that tumor progression may enhance the immunoregulatory response and hence emphasize to the effectiveness of vaccination in early stages of tumor growth for avoiding induction of such regulatory responses.

    Item Type: Article
    Subjects: R Medicine > R Medicine (General)
    Divisions: Faculty of Medical Sciences > School of Medicine
    Depositing User: Mr Vahab Moshtaghi
    Date Deposited: 10 Dec 2016 12:18
    Last Modified: 10 Dec 2016 12:18
    URI: http://eprints.semums.ac.ir/id/eprint/563

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