PMID- 32674488 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 12 IP - 7 DP - 2020 Jul 14 TI - Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy. LID - 10.3390/pharmaceutics12070663 [doi] LID - 663 AB - The onset of checkpoint inhibition revolutionized the treatment of cancer. However, studies from the last decade suggested that the sole enhancement of T cell functionality might not suffice to fight malignancies in all individuals. Dendritic cells (DCs) are not only part of the innate immune system, but also generals of adaptive immunity and they orchestrate the de novo induction of tolerogenic and immunogenic T cell responses. Thus, combinatorial approaches addressing DCs and T cells in parallel represent an attractive strategy to achieve higher response rates across patients. However, this requires profound knowledge about the dynamic interplay of DCs, T cells, other immune and tumor cells. Here, we summarize the DC subsets present in mice and men and highlight conserved and divergent characteristics between different subsets and species. Thereby, we supply a resource of the molecular players involved in key functional features of DCs ranging from their sentinel function, the translation of the sensed environment at the DC:T cell interface to the resulting specialized T cell effector modules, as well as the influence of the tumor microenvironment on the DC function. As of today, mostly monocyte derived dendritic cells (moDCs) are used in autologous cell therapies after tumor antigen loading. While showing encouraging results in a fraction of patients, the overall clinical response rate is still not optimal. By disentangling the general aspects of DC biology, we provide rationales for the design of next generation DC vaccines enabling to exploit and manipulate the described pathways for the purpose of cancer immunotherapy in vivo. Finally, we discuss how DC-based vaccines might synergize with checkpoint inhibition in the treatment of malignant diseases. FAU - Amon, Lukas AU - Amon L AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nurnberg, Hartmannstrasse 14, D-91052 Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany. FAU - Hatscher, Lukas AU - Hatscher L AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nurnberg, Hartmannstrasse 14, D-91052 Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany. FAU - Heger, Lukas AU - Heger L AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nurnberg, Hartmannstrasse 14, D-91052 Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany. FAU - Dudziak, Diana AU - Dudziak D AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nurnberg, Hartmannstrasse 14, D-91052 Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany. AD - Medical Immunology Campus Erlangen, D-91054 Erlangen, Germany. FAU - Lehmann, Christian H K AU - Lehmann CHK AUID- ORCID: 0000-0001-5927-9761 AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nurnberg, Hartmannstrasse 14, D-91052 Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany. AD - Medical Immunology Campus Erlangen, D-91054 Erlangen, Germany. LA - eng GR - RTG2504-B2/Deutsche Forschungsgemeinschaft/ GR - CRC1181-A7/Deutsche Forschungsgemeinschaft/ GR - DU548/5-1/Deutsche Forschungsgemeinschaft/ GR - DU548/6-1/Agency national research (ANR) & Deutsche Forschungsgemeinschaft/ GR - J54/Interdisziplinares Zentrum fur klinische Forschung, Erlangen/ GR - A87/Interdisziplinares Zentrum fur klinische Forschung, Erlangen/ GR - A80/Interdisziplinares Zentrum fur klinische Forschung, Erlangen/ GR - BIG THERA/Emerging Fields Initiative (EFI)/ GR - IRIS/BayResq.Net/ PT - Journal Article PT - Review DEP - 20200714 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC7408110 OTO - NOTNLM OT - T cells OT - antigen targeting OT - cancer therapy OT - checkpoint inhibition OT - dendritic cells OT - pattern recognition receptors OT - tumor microenvironment OT - vaccination COIS- The authors declare no conflict of interest. EDAT- 2020/07/18 06:00 MHDA- 2020/07/18 06:01 PMCR- 2020/07/01 CRDT- 2020/07/18 06:00 PHST- 2020/06/03 00:00 [received] PHST- 2020/06/29 00:00 [revised] PHST- 2020/07/04 00:00 [accepted] PHST- 2020/07/18 06:00 [entrez] PHST- 2020/07/18 06:00 [pubmed] PHST- 2020/07/18 06:01 [medline] PHST- 2020/07/01 00:00 [pmc-release] AID - pharmaceutics12070663 [pii] AID - pharmaceutics-12-00663 [pii] AID - 10.3390/pharmaceutics12070663 [doi] PST - epublish SO - Pharmaceutics. 2020 Jul 14;12(7):663. doi: 10.3390/pharmaceutics12070663.