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Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity
 
 
Review

Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy

by 1,2,3, 1,2,3, 1,2,3, 1,2,3,4,*,† and 1,2,3,4,*,†
1
Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, Germany
2
Deutsches Zentrum Immuntherapie (DZI), D-91054 Erlangen, Germany
3
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), D-91054 Erlangen, Germany
4
Medical Immunology Campus Erlangen, D-91054 Erlangen, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(7), 663; https://doi.org/10.3390/pharmaceutics12070663
Received: 3 June 2020 / Revised: 29 June 2020 / Accepted: 4 July 2020 / Published: 14 July 2020
(This article belongs to the Special Issue Dendritic Cell Vaccines)
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. View Full-Text
Keywords: dendritic cells; T cells; cancer therapy; checkpoint inhibition; antigen targeting; vaccination; pattern recognition receptors; tumor microenvironment dendritic cells; T cells; cancer therapy; checkpoint inhibition; antigen targeting; vaccination; pattern recognition receptors; tumor microenvironment
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MDPI and ACS Style

Amon, L.; Hatscher, L.; Heger, L.; Dudziak, D.; Lehmann, C.H.K. Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy. Pharmaceutics 2020, 12, 663. https://doi.org/10.3390/pharmaceutics12070663

AMA Style

Amon L, Hatscher L, Heger L, Dudziak D, Lehmann CHK. Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy. Pharmaceutics. 2020; 12(7):663. https://doi.org/10.3390/pharmaceutics12070663

Chicago/Turabian Style

Amon, Lukas, Lukas Hatscher, Lukas Heger, Diana Dudziak, and Christian H. K. Lehmann. 2020. "Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy" Pharmaceutics 12, no. 7: 663. https://doi.org/10.3390/pharmaceutics12070663

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