Protinádorová vakcinace dendritickými buňkami v dětské onkologii je studována dvě desetiletí. Většina dosavadních prací je zaměřena na pacienty v pozdních stadiích nádorové nemoci, kteří jsou silně předléčeni imunosupresivní terapií. Přesto jsou pozorovány jednak laboratorní známky protinádorové odpovědi humorální i buněčné, a také klinické odpovědi a benefit pro pacienta. Reprodukovatelnost výsledků je limitována velmi pestrými vstupními kritérii a podmínkami výroby i aplikace vakcín. Další směry vývoje jsou kombinované - léčba s metronomickou terapií nutnou k omezení supresivních funkcí T-regulačních lymfocytů, konkomitance s „checkpoint“ inhibitory, popř. antiangiogenními léčivy a podání vakcíny pacientům v časnější fázi vysoce rizikového nádoru po dosažení léčebné odpovědi na konvenční léčbu. Shrnuty jsou zkušenosti s prvním klinickým hodnocením s dendritickou vakcínou u dětí v České republice.

Immunotherapies with dendritic cell vaccines are studied for two decades in children with high risk tumors. Majority of subjects are at late stage of disease and heavily pretreated with immunosupresive therapies. Despite this, laboratory signs of response in humoral and cellular immunity and clinical benefit rate and objective responses are observed. The comparison between studies is limited due to different inclusion criteria, diseases and designs of vaccine manufacturing and route of administration. Further research will be focused on depletion of T regulatory lymphocytes by either metronomic low dose chemotherapy or concomitant treatment with immune check-point inhibitors. High risk subjects early after induction treatment with tumor response to conventional therapies will be included. The first clinical trial experience of treatment with dendritic cell vaccine in children in Czech Republic is discussed.

• MeSH
• Biomedical Research MeSH
• Dendritic Cells * immunology   classification   MeSH
• Glioma drug therapy   immunology   therapy   MeSH
• Immunotherapy * methods   trends   MeSH
• Combined Modality Therapy methods   trends   MeSH
• Medical Oncology methods   trends   MeSH
• Humans MeSH
• Neuroblastoma drug therapy   immunology   therapy   MeSH
• Pediatrics methods   trends   MeSH
• Cancer Vaccines * therapeutic use   MeSH
• Sarcoma drug therapy   immunology   therapy   MeSH
• Statistics as Topic MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Immunotherapy, Active MeSH
• CTLA-4 Antigen drug effects   MeSH
• Programmed Cell Death 1 Receptor drug effects   MeSH
• Cytokines immunology   classification   MeSH
• Dendritic Cells immunology   classification   MeSH
• Vaccines, DNA MeSH
• Immune System MeSH
• Immunomodulation * immunology   drug effects   MeSH
• Immunotherapy, Adoptive MeSH
• Immunotherapy * classification   methods   utilization   MeSH
• Ipilimumab MeSH
• Medical Oncology * methods   manpower   trends   MeSH
• Humans MeSH
• Melanoma diagnosis   drug therapy   complications   MeSH
• Neoplasm Metastasis diagnosis   drug therapy   MeSH
• Antibodies, Monoclonal administration & dosage   pharmacology   therapeutic use   MeSH
• Kidney Neoplasms diagnosis   drug therapy   complications   MeSH
• Carcinoma, Non-Small-Cell Lung diagnosis   drug therapy   complications   MeSH
• Nivolumab MeSH
• Nobel Prize MeSH
• Check Tag
• Humans MeSH
• Publication type
• Introductory Journal Article MeSH

Alogenní transplantace kmenových buněk krvetvorby (HSCT) je příležitostí ke sledování kinetiky rekonstituce dendritických buněk (DC) a její dynamiky za různých patologií. V této práci jsme analyzovali rekonstituci DC po myeloablativní HSCT. Monitorace probíhala od nejčasnější fáze hematopoetické rekonstituce do D+365 po transplantaci. Myeloidní i plazmacytoidní DC se objevily v nejčasnějších stádiích popřihojení štěpu, jejich relativní podíl v rámci bílých krvinek byl nejvyšší mezi D+19 a D+25 po HSCT a poté jejich proporce klesala. Pacient i s akutní reakcí štěpu proti hostiteli (aGVHD) měli výrazně nižší počet cirkulujících dendritických buněk. Pokles počtu DC předcházel nástupu klinických symptomů nejméně o 24 hodin a byl nezávislý na podávání kortikosteroidů . Kvantifikace plazmacytoidních a myeloidních DC tedy může sloužit jako pomocné vyšetření upozorňující na rozvoj akutní GVHD.

Allogeneic hematopoetic stem cell transplantation (HSCT) represents a unique opportunity to monitor the kinetics of reconstitut ion of dendritic cells (DCs) and their dynamics in distinct pathologies. We analyzed DCs reconstitution after myeloablative HSCT. We separately analyzed patients with acute GVHD. DCs were monitored from the earliest phase of hematopoetic reconstitution until day +365. Both myeloi d DCs and plasmacytoid DCs appeared at earliest stages after engraftment and relative numbers within white blood cells compartment peaked between days 19-25 after HSCT. Their proportion then gradually declined and absolute numbers of both DC subsets remained lower than in contr ols during the whole follow-up. Patients with acute GVHD had significantly lower numbers of circulating DCs. Decrease in DC counts precede d onset of clinical symptoms by at least 24h and was independent of corticosteroids administration. This study reveals quantification of p lasmacytoid and myeloid DCs as a potential biomarker for the prediction of acute GVHD development.

• Keywords
• kortikosteroidy,
• MeSH
• Acute Disease MeSH
• Dendritic Cells immunology   classification   drug effects   MeSH
• Child MeSH
• Financing, Organized MeSH
• Glucocorticoids administration & dosage   pharmacology   MeSH
• Transplantation, Homologous MeSH
• Humans MeSH
• Adolescent MeSH
• Flow Cytometry methods   utilization   MeSH
• Graft vs Host Reaction MeSH
• Hematopoietic Stem Cell Transplantation methods   utilization   MeSH
• Bone Marrow Transplantation MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH

Human dendritic cells have distinct roles in the regulation of immunity. In this study we analysed the kinetics and the proportion of myeloid and plasmacytoid subsets of dendritic cells (DC) in peripheral blood of 15 patients with multiple myeloma (MM) before and during treatment that included autologous transplantation. Control group of 15 healthy volunteers was evaluated by using the same approaches. Flowcytometric determination of relative and absolute cell counts in unmanipulated peripheral blood was based on the expression of surface antigens CD83 and HLA-DR. Depending on the expression of CD11c or CD123, we divided these cells into CD11c+ dendritic cells type 1 (DC1) and CD123+ DC type 2 (DC2). Significant differences were found in initial relative counts of CD83+ cells and of the DC2 subtype between the group of controls and the group of patients before treatment. In absolute counts, there was a difference only in the DC2 subtype. After induction treatment (vincristine, doxorubicin, and dexamethasone), the mean percentage of CD83+ DC and the DC1 percentage were significantly higher than initially, but there was no significant difference in absolute counts. Administration of G-CSF again increased the total DC numbers. Intermediate DC counts were found in the apheresis products. After engraftment, we found the highest relative DC numbers, but absolute counts were not very high because of leukopenia. Within six months after transplantation, normal relative and absolute DC counts were found in patients. Untreated patients with MM have significantly lower relative numbers of peripheral blood DC in comparison with healthy volunteers. The highest number of total DC was found after engraftment. The DC1/DC2 ratio showed relative predominance of DC1 subtype and the lowest DC1/DC2 ratio was found in the apheresis products. DC counts comparable with those of healthy volunteers were found in patients six months after transplantation.

• MeSH
• CD11c Antigen metabolism   MeSH
• Transplantation, Autologous MeSH
• Time Factors MeSH
• Antigens, CD metabolism   MeSH
• Dendritic Cells cytology   classification   MeSH
• Dexamethasone administration & dosage   MeSH
• Doxorubicin administration & dosage   MeSH
• Granulocyte Colony-Stimulating Factor administration & dosage   MeSH
• Financing, Organized MeSH
• HLA-DR Antigens metabolism   MeSH
• Immunoglobulins metabolism   MeSH
• Remission Induction MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Membrane Glycoproteins metabolism   MeSH
• Multiple Myeloma immunology   metabolism   therapy   MeSH
• Cell Count MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Flow Cytometry MeSH
• Interleukin-3 Receptor alpha Subunit metabolism   MeSH
• Peripheral Blood Stem Cell Transplantation MeSH
• Vincristine administration & dosage   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH

• MeSH
• Antigens, Neoplasm immunology   MeSH
• Apoptosis MeSH
• Dendritic Cells immunology   classification   transplantation   MeSH
• Hematologic Neoplasms immunology   therapy   MeSH
• Hodgkin Disease immunology   therapy   MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Cancer Vaccines therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH

• MeSH
• Autoimmunity MeSH
• Dendritic Cells physiology   classification   MeSH
• Immunotherapy MeSH
• Humans MeSH
• Neoplasms MeSH
• Antigen Presentation physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Review MeSH