Medical Oncology

, Volume 28, Supplement 1, pp 660–666 | Cite as

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

  • Morteza Samadi-Foroushani
  • Rouhollah Vahabpour
  • Arash Memarnejadian
  • Afshin Namdar
  • Masoumeh Khamisabadi
  • Seyed Mehdi Sadat
  • Hossein Asgarian-Omran
  • Kayhan Azadmanesh
  • Parviz Kokhaei
  • Mohammad Reza Aghasadeghi
  • Jamshid Hadjati
Original Paper

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 cell Regulatory T cell Foxp3 IDO Tumor immunotherapy 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Morteza Samadi-Foroushani
    • 1
  • Rouhollah Vahabpour
    • 2
  • Arash Memarnejadian
    • 2
  • Afshin Namdar
    • 1
  • Masoumeh Khamisabadi
    • 1
  • Seyed Mehdi Sadat
    • 2
  • Hossein Asgarian-Omran
    • 1
  • Kayhan Azadmanesh
    • 2
  • Parviz Kokhaei
    • 3
    • 4
  • Mohammad Reza Aghasadeghi
    • 2
  • Jamshid Hadjati
    • 1
  1. 1.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Pasteur Institute of IranTehranIran
  3. 3.Department of ImmunologySemnan University of Medical SciencesSemnanIran
  4. 4.Immune and Gene Therapy Lab. CCKKarolinska University HospitalSolna, StockholmSweden

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