PMID- 30999964 OWN - NLM STAT- MEDLINE DCOM- 20200707 LR - 20231011 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 7 IP - 1 DP - 2019 Apr 18 TI - The clinical application of cancer immunotherapy based on naturally circulating dendritic cells. PG - 109 LID - 10.1186/s40425-019-0580-6 [doi] LID - 109 AB - Dendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation. One possible explanation for this is that the most commonly used monocyte-derived DCs may not be the best source for DC-based immunotherapy. The novel approach to use naturally circulating DCs may be an attractive alternative. In contrast to monocyte-derived DCs, naturally circulating DCs are relatively scarce but do not require extensive culture periods. Thereby, their functional capabilities are preserved, the reproducibility of clinical applications is increased, and the cells are not dysfunctional before injection. In human blood, at least three DC subsets can be distinguished, plasmacytoid DCs, CD141(+) and CD1c(+) myeloid/conventional DCs, each with distinct functional characteristics. In completed clinical trials, either CD1c(+) myeloid DCs or plasmacytoid DCs were administered and showed encouraging immunological and clinical outcomes. Currently, also the combination of CD1c(+) myeloid and plasmacytoid DCs as well as the intratumoral use of CD1c(+) myeloid DCs is under investigation in the clinic. Isolation and culture strategies for CD141(+) myeloid DCs are being developed. Here, we summarize and discuss recent clinical developments and future prospects of natural DC-based immunotherapy. FAU - Bol, Kalijn F AU - Bol KF AD - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. AD - Department of Medical Oncology, Radboud university medical centre, Nijmegen, the Netherlands. FAU - Schreibelt, Gerty AU - Schreibelt G AD - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. FAU - Rabold, Katrin AU - Rabold K AD - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. AD - Radiotherapy & OncoImmunology Laboratory, Radboud university medical centre, Nijmegen, the Netherlands. FAU - Wculek, Stefanie K AU - Wculek SK AD - Immunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares ;Carlos III;, Madrid, Spain. FAU - Schwarze, Julia Katharina AU - Schwarze JK AD - Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium. FAU - Dzionek, Andrzej AU - Dzionek A AD - Miltenyi Biotec GmbH, Bergisch-Gladbach, Germany. FAU - Teijeira, Alvaro AU - Teijeira A AD - Center for Applied Medical Research, University of Navarra, Pamplona, Spain. FAU - Kandalaft, Lana E AU - Kandalaft LE AD - Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. FAU - Romero, Pedro AU - Romero P AD - Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. FAU - Coukos, George AU - Coukos G AD - Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. FAU - Neyns, Bart AU - Neyns B AD - Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium. FAU - Sancho, David AU - Sancho D AD - Immunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares ;Carlos III;, Madrid, Spain. FAU - Melero, Ignacio AU - Melero I AD - Center for Applied Medical Research, University of Navarra, Pamplona, Spain. AD - CIBERONC, Madrid, Spain. FAU - de Vries, I Jolanda M AU - de Vries IJM AD - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Jolanda.deVries@radboudumc.nl. AD - Department of Medical Oncology, Radboud university medical centre, Nijmegen, the Netherlands. Jolanda.deVries@radboudumc.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190418 PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Antigens, CD1) RN - 0 (CD1C protein, human) RN - 0 (Cancer Vaccines) RN - 0 (Glycoproteins) SB - IM MH - *Adaptive Immunity MH - Antigens, CD1/immunology/metabolism MH - Cancer Vaccines/immunology/*therapeutic use MH - Cell Culture Techniques/methods MH - Clinical Trials as Topic MH - Dendritic Cells/immunology/metabolism/*transplantation MH - Glycoproteins/immunology/metabolism MH - Humans MH - Immunotherapy/*methods/trends MH - Neoplasms/immunology/*therapy MH - Treatment Outcome PMC - PMC6471787 OTO - NOTNLM OT - Cancer OT - Conventional dendritic cells OT - Cross-presenting dendritic cells OT - Dendritic cells OT - Immunotherapy OT - Myeloid dendritic cells OT - Natural dendritic cells OT - Plasmacytoid dendritic cells OT - Vaccination COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: AD is an employee of Miltenyi Biotec. All other authors declare no conflict of interest. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/04/20 06:00 MHDA- 2020/07/08 06:00 PMCR- 2019/04/18 CRDT- 2019/04/20 06:00 PHST- 2019/02/11 00:00 [received] PHST- 2019/03/26 00:00 [accepted] PHST- 2019/04/20 06:00 [entrez] PHST- 2019/04/20 06:00 [pubmed] PHST- 2020/07/08 06:00 [medline] PHST- 2019/04/18 00:00 [pmc-release] AID - 10.1186/s40425-019-0580-6 [pii] AID - 580 [pii] AID - 10.1186/s40425-019-0580-6 [doi] PST - epublish SO - J Immunother Cancer. 2019 Apr 18;7(1):109. doi: 10.1186/s40425-019-0580-6.