Medical Oncology

, Volume 28, Supplement 1, pp 660–666

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

Authors

  • Morteza Samadi-Foroushani
    • Department of Immunology, School of MedicineTehran University of Medical Sciences
  • Rouhollah Vahabpour
    • Pasteur Institute of Iran
  • Arash Memarnejadian
    • Pasteur Institute of Iran
  • Afshin Namdar
    • Department of Immunology, School of MedicineTehran University of Medical Sciences
  • Masoumeh Khamisabadi
    • Department of Immunology, School of MedicineTehran University of Medical Sciences
  • Seyed Mehdi Sadat
    • Pasteur Institute of Iran
  • Hossein Asgarian-Omran
    • Department of Immunology, School of MedicineTehran University of Medical Sciences
  • Kayhan Azadmanesh
    • Pasteur Institute of Iran
  • Parviz Kokhaei
    • Department of ImmunologySemnan University of Medical Sciences
    • Immune and Gene Therapy Lab. CCKKarolinska University Hospital
  • Mohammad Reza Aghasadeghi
    • Pasteur Institute of Iran
    • Department of Immunology, School of MedicineTehran University of Medical Sciences
Original Paper

DOI: 10.1007/s12032-010-9720-z

Cite this article as:
Samadi-Foroushani, M., Vahabpour, R., Memarnejadian, A. et al. Med Oncol (2011) 28: 660. doi:10.1007/s12032-010-9720-z
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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.

Keywords

Dendritic cellRegulatory T cellFoxp3IDOTumor immunotherapy

Copyright information

© Springer Science+Business Media, LLC 2010