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Erschienen in: Medical Oncology 1/2011

01.12.2011 | Original Paper

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

verfasst von: 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

Erschienen in: Medical Oncology | Sonderheft 1/2011

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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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Metadaten
Titel
Immune responses regulation following antitumor dendritic cell-based prophylactic, concurrent, and therapeutic vaccination
verfasst von
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
Publikationsdatum
01.12.2011
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe Sonderheft 1/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9720-z

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