Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/7/663 |
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| author | Lukas Amon Lukas Hatscher Lukas Heger Diana Dudziak Christian H. K. Lehmann |
| author_facet | Lukas Amon Lukas Hatscher Lukas Heger Diana Dudziak Christian H. K. Lehmann |
| author_sort | Lukas Amon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:28:42Z |
| format | Article |
| id | doaj.art-7cb4926558a84b5d9545a337e3f97c0b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T18:28:42Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7cb4926558a84b5d9545a337e3f97c0b2023-11-20T06:46:35ZengMDPI AGPharmaceutics1999-49232020-07-0112766310.3390/pharmaceutics12070663Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer ImmunotherapyLukas Amon0Lukas Hatscher1Lukas Heger2Diana Dudziak3Christian H. K. Lehmann4Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, GermanyLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, GermanyLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, GermanyLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, GermanyLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstraße 14, D-91052 Erlangen, GermanyThe 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.https://www.mdpi.com/1999-4923/12/7/663dendritic cellsT cellscancer therapycheckpoint inhibitionantigen targetingvaccination |
| spellingShingle | Lukas Amon Lukas Hatscher Lukas Heger Diana Dudziak Christian H. K. Lehmann Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy Pharmaceutics dendritic cells T cells cancer therapy checkpoint inhibition antigen targeting vaccination |
| title | Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy |
| title_full | Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy |
| title_fullStr | Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy |
| title_full_unstemmed | Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy |
| title_short | Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy |
| title_sort | harnessing the complete repertoire of conventional dendritic cell functions for cancer immunotherapy |
| topic | dendritic cells T cells cancer therapy checkpoint inhibition antigen targeting vaccination |
| url | https://www.mdpi.com/1999-4923/12/7/663 |
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