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Immune responses regulation following antitumor dendritic cell-based prophylactic, concurrent, and therapeutic vaccination

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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.

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Acknowledgments

This research has been supported by Tehran University of Medical Sciences and Health Services (Grant number: 86-03-30-6154).

Conflict of interest

Authors have no actual or potential conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Poorsina Avenue, Tehran, Iran

    Morteza Samadi-Foroushani, Afshin Namdar, Masoumeh Khamisabadi, Hossein Asgarian-Omran & Jamshid Hadjati

  2. Pasteur Institute of Iran, Tehran, Iran

    Rouhollah Vahabpour, Arash Memarnejadian, Seyed Mehdi Sadat, Kayhan Azadmanesh & Mohammad Reza Aghasadeghi

  3. Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran

    Parviz Kokhaei

  4. Immune and Gene Therapy Lab. CCK, Karolinska University Hospital, Solna, Stockholm, Sweden

    Parviz Kokhaei

Authors
  1. Morteza Samadi-Foroushani
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  2. Rouhollah Vahabpour
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  3. Arash Memarnejadian
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  4. Afshin Namdar
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  5. Masoumeh Khamisabadi
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  7. Hossein Asgarian-Omran
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  8. Kayhan Azadmanesh
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  9. Parviz Kokhaei
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  10. Mohammad Reza Aghasadeghi
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  11. Jamshid Hadjati
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Correspondence to Jamshid Hadjati.

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Samadi-Foroushani, M., Vahabpour, R., Memarnejadian, A. et al. Immune responses regulation following antitumor dendritic cell-based prophylactic, concurrent, and therapeutic vaccination. Med Oncol 28 (Suppl 1), 660–666 (2011). https://doi.org/10.1007/s12032-010-9720-z

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  • DOI: https://doi.org/10.1007/s12032-010-9720-z

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