Immune responses regulation following antitumor dendritic cell-based prophylactic, concurrent, and therapeutic vaccination.
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.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Poorsina Avenue, Tehran, Iran.
Morteza
M
Samadi-Foroushani
Rouhollah
R
Vahabpour
Arash
A
Memarnejadian
Afshin
A
Namdar
Masoumeh
M
Khamisabadi
Seyed Mehdi
SM
Sadat
Hossein
H
Asgarian-Omran
Kayhan
K
Azadmanesh
Parviz
P
Kokhaei
Mohammad Reza
MR
Aghasadeghi
Jamshid
J
Hadjati
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines