Effect of prostaglandin E2, lipopolysaccharide, IFN-γ and cytokines on the generation and function of fast-DC

Alldawi, Louie; Takahashi, Motoki; Narita, Miwako; Ayres, Flávio Monteiro; Tsukada, Naoyuki; Osman, Yasser; Furukawa, Tatsuo; Aizawa, Yoshifusa

doi:10.1080/14653240510018127

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…Monocytes were selected from blood of healthy volunteers (HV) or cancer patients (GBM, glioblastoma multiforme LYM, B-cell lymphoma; RCC, renal cell carcinoma; SR, sarcoma) by CD14 + immunomagnetic beads and cultured under different methods as labeled in X axis. Method A, fast-DC (28); B, ex vivo media with 5 days culture as described (29, 30); C, 5 days culture in StemLine media and GM-CSF, maturation factors TNFα and PGE2 added in the last 2 days of culture; D, method C with IL-4 added for 5 days of culture; E, method D with poly I:C added to maturation factors; F, method D with CpG used as maturation factor in place of TNF-α (* p < 0.05). (C) Decreased generation of mDC correlates with increased percentage of CD14 + HLA-DR lo/neg in the monocytes selected for culture (Method B).…”

Section: Monocyte Precursors Of DC Are Often Altered In Cancer Patienmentioning

confidence: 99%

“…Non-adherent cells were collected on day 6, re-suspended in base media with the addition of tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) to mature the DCs. This recipe is based on a classic method of generation of mDCs (28, 29, 41). Alternatively, the system was modified using a serum-free media and changes in cytokines to generate mDCs (Figure 1B).…”

Section: Monocyte Precursors Of DC Are Often Altered In Cancer Patienmentioning

confidence: 99%

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Cancer Vaccines in the World of Immune Suppressive Monocytes (CD14+HLA-DRlo/neg Cells): The Gateway to Improved Responses

et al. 2014

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Dendritic cells are an important target in cancer immunotherapy based on their critical role in antigen presentation and response to tumor development. The capacity of dendritic cells to stimulate anti-tumor immunity has led investigators to use these cells to mediate anti-tumor responses in a number of clinical trials. However, these trials have had mixed results. The typical method for generation of ex vivo dendritic cells starts with the purification of CD14+ cells. Our studies identified a deficiency in the ability to generate mature dendritic cell using CD14+ cells from cancer patients that corresponded with an increased population of monocytes with altered surface marker expression (CD14+HLA-DRlo/neg). Further studies identified systemic immune suppression and increased concentrations of CD14+HLA-DRlo/neg monocytes capable of inhibiting T-cell proliferation and DC maturation. Together, these findings strongly suggest that protocols aimed at immune stimulation via monocytes/dendritic cells, if optimized on normal monocytes or in systems without these suppressive monocytes, are unlikely to engender effective DC maturation in vitro or efficiently trigger DC maturation in vivo. This highlights the importance of developing optimal protocols for stimulating DCs in the context of significantly altered monocyte phenotypes often seen in cancer patients.

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Section: Monocyte Precursors Of DC Are Often Altered In Cancer Patienmentioning

confidence: 99%

Section: Monocyte Precursors Of DC Are Often Altered In Cancer Patienmentioning

confidence: 99%

Cancer Vaccines in the World of Immune Suppressive Monocytes (CD14+HLA-DRlo/neg Cells): The Gateway to Improved Responses

et al. 2014

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“…Those DCs were able to induce tetanus toxoid specific T cells. Alldawi et al (10) reported on DCs generated in 48 h using GM-CSF, IL-4 and LPS and INF-Á. Recently, Dauer et al (23) reported that DCs developed in 48 h primed CTLs using Melan-A/HLA-A0201 peptide.…”

Section: Discussionmentioning

confidence: 99%

“…However, some reports indicated that there is some dissociation of the period required for generation of DCs between experimental in vitro and in vivo model. Functional DCs have been reported to mature from monocytes after 48 h culture of peripheral blood mononuclear cells (PBMCs) in the presence of GM-CSF and IL-4 (9,10). However, whether or not these short-term cultured DCs have an ability to encounter naïve T cells and initiate an adoptive cellular immune response remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes

et al. 2006

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Abstract. Dendritic cells (DCs) are powerful antigenpresenting cells (APCs), that have so far been applied for cancer specific immunotherapy. Recent results suggest that matured DCs derived from human monocytes have a significant impact on the outcome of vaccination. The conventional generation of mature DCs from human monocytes in vitro has been reported to require 5 days for differentiation with granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 2 days for stimulation. We herein report a new strategy for the functional maturation of monocyte-derived DCs within only 2 days of in vitro culture and the induction of specific cytotoxic T lymphocytes (CTLs) to tumor rejection peptide. The monocytes were incubated for 1 day with GM-CSF and IL-4, followed by activation with a bacterial product, OK-432 and prostaglandin E 2 (PGE 2 ) for another 1 day (rapid DC). Rapid DC expressed mature DC surface markers as well as chemokine receptor 7 and secreted Th1-type cytokines. The DCs genereated in this study mobilized Ca 2+ in response to CCL21/6Ckine and SDF-1, but only marginally did so to Mip-1·. Moreover, when rapid DC were compared with mature conventional 7-day DCs, they were equally potent in inducing specific CTLs in vitro. These results indicate that the rapid DC is as effective as the monocyte-derived conventional DCs. The rapid DC would be a potentially useful new cancer-specific immunotherapy.

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“…1. Because circulating DCs represent ,1% of the total cell population in human peripheral blood, we used monocytes known to be a usual progenitor for the in vitro generation of iDCs when cultured with a cytokine mixture made of GM-CSF and IL-4 (26)(27)(28)(29). For the purpose of our study, monocytes were separated from PBMCs by cell adherence as described previously (30,31).…”

Section: Resultsmentioning

confidence: 99%

Dendritic Cells Derived from Hemozoin-Loaded Monocytes Display a Partial Maturation Phenotype that Promotes HIV-1 Trans-Infection of CD4+ T Cells and Virus Replication

Diou

Tardif

Barat

et al. 2010

The Journal of Immunology

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Coinfection of HIV-1 patients with Plasmodium falciparum, the etiological agent of malaria, results in a raise of viral load and an acceleration of disease progression. The primary objective of this study was to investigate whether the malarial pigment hemozoin (HZ), a heme by-product of hemoglobin digestion by malaria parasites, can affect HIV-1 transmission by monocytes-derived dendritic cells (DCs) to CD4+ T cells when HZ is initially internalized in monocytes before their differentiation in DCs. We demonstrate in this study that HZ treatment during the differentiation process induces an intermediate maturation phenotype when compared with immature and fully mature DCs. Furthermore, the DC-mediated transfer of HIV-1 is enhanced in presence of HZ, a phenomenon that may be linked with the capacity of HZ-loaded cells to interact and activate CD4+ T cells. Altogether our findings suggest a new mechanism that could partially explain the increased HIV-1 virus production during a coinfection with P. falciparum. Understanding the multifaceted interactions between P. falciparum and HIV-1 is an important challenge that could lead to the development of new treatment strategies.

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Effect of prostaglandin E2, lipopolysaccharide, IFN-γ and cytokines on the generation and function of fast-DC

Cited by 10 publications

References 21 publications

Cancer Vaccines in the World of Immune Suppressive Monocytes (CD14+HLA-DRlo/neg Cells): The Gateway to Improved Responses

Cancer Vaccines in the World of Immune Suppressive Monocytes (CD14+HLA-DRlo/neg Cells): The Gateway to Improved Responses

Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes

Dendritic Cells Derived from Hemozoin-Loaded Monocytes Display a Partial Maturation Phenotype that Promotes HIV-1 Trans-Infection of CD4+ T Cells and Virus Replication

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