PMID- 30764500 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 11 IP - 2 DP - 2019 Feb 5 TI - Cord-Blood-Stem-Cell-Derived Conventional Dendritic Cells Specifically Originate from CD115-Expressing Precursors. LID - 10.3390/cancers11020181 [doi] LID - 181 AB - Dendritic cells (DCs) are professional antigen-presenting cells which instruct both the innate and adaptive immune systems. Once mature, they have the capacity to activate and prime naive T cells for recognition and eradication of pathogens and tumor cells. These characteristics make them excellent candidates for vaccination strategies. Most DC vaccines have been generated from ex vivo culture of monocytes (mo). The use of mo-DCs as vaccines to induce adaptive immunity against cancer has resulted in clinical responses but, overall, treatment success is limited. The application of primary DCs or DCs generated from CD34(+) stem cells have been suggested to improve clinical efficacy. Cord blood (CB) is a particularly rich source of CD34(+) stem cells for the generation of DCs, but the dynamics and plasticity of the specific DC lineage development are poorly understood. Using flow sorting of DC progenitors from CB cultures and subsequent RNA sequencing, we found that CB-derived DCs (CB-DCs) exclusively originate from CD115(+)-expressing progenitors. Gene set enrichment analysis displayed an enriched conventional DC profile within the CD115-derived DCs compared with CB mo-DCs. Functional assays demonstrated that these DCs matured and migrated upon good manufacturing practice (GMP)-grade stimulation and possessed a high capacity to activate tumor-antigen-specific T cells. In this study, we developed a culture protocol to generate conventional DCs from CB-derived stem cells in sufficient numbers for vaccination strategies. The discovery of a committed DC precursor in CB-derived stem cell cultures further enables utilization of conventional DC-based vaccines to provide powerful antitumor activity and long-term memory immunity. FAU - Plantinga, Maud AU - Plantinga M AD - Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. m.c.plantinga-2@umcutrecht.nl. FAU - de Haar, Colin G AU - de Haar CG AD - Cell Therapy Facility, Pharmacy Department, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. c.g.dehaar@umcutrecht.nl. FAU - Dunnebach, Ester AU - Dunnebach E AD - Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. E.dunnebach-2@umcutrecht.nl. FAU - van den Beemt, Denise A M H AU - van den Beemt DAMH AD - Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. d.a.m.vandenbeemt@umcutrecht.nl. FAU - Bloemenkamp, Kitty W M AU - Bloemenkamp KWM AD - Division Woman and Baby, Department of Obstetrics, University Medical Center Utrecht, Birth Center Wilhelmina's Children Hospital, 3584 EA Utrecht, The Netherlands. K.W.M.Bloemenkamp@umcutrecht.nl. FAU - Mokry, Michal AU - Mokry M AD - Division of Pediatrics, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands. M.Mokry@umcutrecht.nl. FAU - Boelens, Jaap Jan AU - Boelens JJ AUID- ORCID: 0000-0003-2232-6952 AD - Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. boelensj@mskcc.org. AD - Blood and Marrow Transplantation Program, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands. boelensj@mskcc.org. AD - Stem Cell Transplant and Cellular Therapies, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. boelensj@mskcc.org. FAU - Nierkens, Stefan AU - Nierkens S AUID- ORCID: 0000-0003-3406-817X AD - Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 XC Utrecht, The Netherlands. s.nierkens@umcutrecht.nl. AD - Blood and Marrow Transplantation Program, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands. s.nierkens@umcutrecht.nl. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R4169/KWF Kankerbestrijding/ PT - Journal Article DEP - 20190205 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC6406310 OTO - NOTNLM OT - DC precursor OT - DC subsets OT - cancer OT - cord blood OT - dendritic cell OT - vaccine COIS- The authors declare no conflicts of interest and the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2019/02/16 06:00 MHDA- 2019/02/16 06:01 PMCR- 2019/02/05 CRDT- 2019/02/16 06:00 PHST- 2018/12/10 00:00 [received] PHST- 2019/01/30 00:00 [revised] PHST- 2019/01/31 00:00 [accepted] PHST- 2019/02/16 06:00 [entrez] PHST- 2019/02/16 06:00 [pubmed] PHST- 2019/02/16 06:01 [medline] PHST- 2019/02/05 00:00 [pmc-release] AID - cancers11020181 [pii] AID - cancers-11-00181 [pii] AID - 10.3390/cancers11020181 [doi] PST - epublish SO - Cancers (Basel). 2019 Feb 5;11(2):181. doi: 10.3390/cancers11020181.