Paricalcitol (19-nor-1,25/OH(2)/D(2)), a second generation vitamin D receptor (VDR) activator, is a synthetic analogue of vitamin D3. In contrast to calcitriol, paricalcitol has a reduced effect on intestinal calcium resorption thus avoiding undesirable hypercalcemia. Information about immunomodulatory activity of paricalcitol is scarce. In this study we show that, in all investigated aspects, paricalcitol retains significant immunomodulatory activity, comparable to calcitriol. Both VDR agonists impaired differentiation of immature dendritic cells (DCs) from monocytes. The presence of VDR agonists during DC differentiation abolished their capacity to be activated and, despite potent Toll-like receptor mediated stimulation, VDR agonist-treated DCs remained in the immature state. In accordance with these findings, VDR-treated DCs produced no bioactive IL-12 and had a significantly decreased capacity to induce antigen-specific T cells while the capacity to induce functional Tregs remained unchanged when compared to control DCs. As DCs and T cells play an important role in the pathogenesis of atherosclerosis, in end-stage renal disease patients, paricalcitol should be a VDR agonist of choice for the reduction of the risk of atherosclerosis due to its immunomodulatory effect proven in this study and known limited hypercalcemic effect. The immunomodulatory potency of paricalcitol makes it a drug of interest in the therapy of chronic immune-mediated inflammatory diseases.
- MeSH
- aktivace lymfocytů účinky léků MeSH
- buněčná diferenciace imunologie účinky léků MeSH
- CD8-pozitivní T-lymfocyty imunologie účinky léků MeSH
- dendritické buňky imunologie účinky léků MeSH
- ergokalciferoly farmakologie MeSH
- imunologické faktory farmakologie MeSH
- interleukin-12 biosyntéza imunologie MeSH
- kalcitriol farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- monocyty imunologie účinky léků MeSH
- receptory kalcitriolu antagonisté a inhibitory MeSH
- regulační T-lymfocyty imunologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Surgery and chemotherapy are standard treatments in ovarian cancer, but patients have a high rate of relapse. Dendritic cell (DC)-based vaccines are a new treatment option for elimination of residual tumor disease. We aim to explore the feasibility and immunogenicity of DC vaccines pulsed with autologous irradiated tumor cells from ovarian cancer patients. Monocyte-derived DC were generated and pulsed with autologous tumor-derived bodies, matured and subsequently cocultured with autologous lymphocytes. The ability of DC to activate lymphocytes was evaluated by proliferation and IFN-gamma ELISPOT. Induction of tumor cell apoptosis was optimal at 24 h, and DC pulsing optimal at 4 h. Maturation of DC and proliferation of lymphocytes were achieved in 75% of patients tested. Lymphocyte IFN-gamma production increased in response to tumor antigen-pulsed DC. We show the feasibility of preparing individual DC-based vaccines in ovarian cancer patients and the potential for induction of lymphocyte responses.
- MeSH
- aktivace lymfocytů imunologie MeSH
- aktivní imunoterapie metody MeSH
- antigeny nádorové imunologie MeSH
- apoptóza fyziologie MeSH
- cytokiny biosyntéza MeSH
- dendritické buňky imunologie MeSH
- dospělí MeSH
- fagocytóza imunologie MeSH
- financování organizované MeSH
- imunoenzymatické techniky MeSH
- interferon gama biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory vaječníků terapie MeSH
- protinádorové vakcíny imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- dendritické buňky cytologie imunologie MeSH
- lidé MeSH
- monocyty imunologie MeSH
- nádory prostaty chirurgie MeSH
- prostatektomie využití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- dendritické buňky transplantace MeSH
- imunoterapie metody využití MeSH
- lidé MeSH
- prostatický specifický antigen terapeutické užití MeSH
- testis MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kongresy MeSH