Original Paper

Medical Oncology

, Volume 28, Supplement 1, pp 660-666

First online:

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

  • Morteza Samadi-ForoushaniAffiliated withDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences
  • , Rouhollah VahabpourAffiliated withPasteur Institute of Iran
  • , Arash MemarnejadianAffiliated withPasteur Institute of Iran
  • , Afshin NamdarAffiliated withDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences
  • , Masoumeh KhamisabadiAffiliated withDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences
  • , Seyed Mehdi SadatAffiliated withPasteur Institute of Iran
  • , Hossein Asgarian-OmranAffiliated withDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences
  • , Kayhan AzadmaneshAffiliated withPasteur Institute of Iran
  • , Parviz KokhaeiAffiliated withDepartment of Immunology, Semnan University of Medical SciencesImmune and Gene Therapy Lab. CCK, Karolinska University Hospital
    • , Mohammad Reza AghasadeghiAffiliated withPasteur Institute of Iran
    • , Jamshid HadjatiAffiliated withDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences Email author 

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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 cell Regulatory T cell Foxp3 IDO Tumor immunotherapy