Article

Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state.

Department of Tumor Immunology, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands.
Cancer Research (Impact Factor: 9.28). 02/2003; 63(1):12-7.
Source: PubMed

ABSTRACT Dendritic cells are the professional antigen-presenting cells of the immune system. To induce an effective immune response, these cells should not only express high levels of MHC and costimulatory molecules but also migrate into the lymph nodes to interact with naïve T cells. Here, we demonstrate that in vitro-generated mature, but not immature dendritic cells, efficiently migrate into the T-cell areas of lymph nodes of melanoma patients. This difference is confirmed by in vitro studies, in which immature dendritic cells are strongly adherent, whereas mature dendritic cells remain highly motile. Our present findings demonstrate that the ability of dendritic cells to mount a proper immune response correlates with their ability to migrate both in vitro and in vivo.

0 Bookmarks
 · 
64 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human placenta-derived adherent cells (PDAC cells) are a culture expanded, undifferentiated mesenchymal-like population derived from full-term placental tissue, with immunomodulatory and anti-inflammatory properties. PDA-001 (cenplacel-L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. To elucidate the mechanisms underlying the immunoregulatory properties of PDAC cells, we investigated their effects on immune cell populations, including T cells and dendritic cells (DC) in vitro and in vivo. PDAC cells suppressed T-cell proliferation in an OT-II T-cell adoptive transfer model, reduced the severity of myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis and ameliorated inflammation in a delayed type hypersensitivity response model. In vitro, PDAC cells suppressed T-cell proliferation and inhibited Th1 and Th17 differentiation. Analysis of tissues derived from PDAC cell-treated animals revealed diminished CD86 expression on splenic DC, suggesting that they can also modulate DC populations. Furthermore, PDAC cells modulate the differentiation and maturation of mouse bone marrow-derived DC. Similarly, human DC differentiated from CD14(+) monocytes in the presence of PDAC cells acquired a tolerogenic phenotype. These tolerogenic DC failed to induce allogeneic T-cell proliferation and differentiation toward Th1, but skewed T-cell differentiation toward Th2. Inhibition of cyclo-oxygenase-2 activity resulted in a significant, but not complete, abrogation of PDAC cells' effects on DC phenotype and function, implying a role for prostaglandin E2 in PDAC-mediated immunomodulation. This study identifies modulation of DC differentiation toward immune tolerance as a key mechanism underlying the immunomodulatory activities of PDAC cells.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is a leading cause of death in women, and almost all complications are due to chemotherapy resistance. Drug-resistant cells with stem cell phenotypes are thought to cause failure in breast cancer chemotherapy. Dendritic cell (DC) therapy is a potential approach to eradicate these cells. This study evaluates the specificity of DCs for breast cancer stem cells (BCSCs) in vitro and in vivo. BCSCs were enriched by a verapamil-resistant screening method, and reconfirmed by ALDH expression analysis and mammosphere assay. Mesenchymal stem cells (MSCs) were isolated from allogeneic murine bone marrow. DCs were induced from bone marrow-derived monocytes with 20 ng/mL GC-MSF and 20 ng/mL IL-4. Immature DCs were primed with BCSC-or MSC-derived antigens to make two kinds of mature DCs: BCSC-DCs and MSC-DCs, respectively. In vitro ability of BCSC-DCs and MSC-DCs with cytotoxic T lymphocytes (CTLs) to inhibit BCSCs was tested using the xCELLigence technique. In vivo, BCSC-DCs and MSC-DCs were transfused into the peripheral blood of BCSC tumor-bearing mice. The results show that in vitro BCSC-DCs significantly inhibited BCSC proliferation at a DC:CTL ratio of 1:40, while MSC-DCs nonsignificantly decreased BCSC proliferation. In vivo, tumor sizes decreased from 18.8% to 23% in groups treated with BCSC-DCs; in contrast, tumors increased 14% in the control group (RPMI 1640) and 47% in groups treated with MSC-DCs. The results showed that DC therapy could target and be specific to BCSCs. DCs primed with MSCs could trigger tumor growth. These results also indicate that DCs may be a promising therapy for treating drug-resistant cancer cells as well as cancer stem cells.
    OncoTargets and Therapy 01/2015; 20158(8):323-334. DOI:10.2147/OTT.S77554 · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An 80-year-old man with a history of gastric cancer and pulmonary emphysema underwent a distal gastrectomy for gastric cancer in 1997. In 2010, an endoscopic examination revealed a depressed-type lesion at the oral side of the anastomosis, which was diagnosed as signet-ring adenocarcinoma. Surgical management was considered, but was rejected because of obstructive and restrictive respiratory events. Chemotherapy was terminated because of adverse events. Endoscopy was used to administer intratumoral injections of dendritic cells (DCs) targeting synthesized peptides of Wilms tumor 1 (WT1) and mucin 1, cell-surface associated (MUC1). An immunohistochemical analysis of the tumor samples indicated positivity for WT1 and MUC1. One month after seven cycles of DC had been administered (between November 2010 and April 2011), no suspicious lesions were evident, and his biopsy results were normal. The patient has been in remission for 30 months. Intratumoral injections of DCs showed therapeutic effects in this patient, who could not undergo endoscopic submucosal dissection or surgery.
    World Journal of Surgical Oncology 12/2014; 12(1):390. DOI:10.1186/1477-7819-12-390 · 1.20 Impact Factor

Full-text (2 Sources)

Download
100 Downloads
Available from
Jun 2, 2014