Cord-Blood-Stem-Cell-Derived Conventional Dendritic Cells Specifically Originate from CD115-Expressing Precursors
Autor: | Ester Dunnebach, Stefan Nierkens, Maud Plantinga, Colin de Haar, Denise A. M. H. van den Beemt, Michal Mokry, Kitty W. M. Bloemenkamp, Jaap Jan Boelens |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research DC subsets dendritic cell chemical and pharmacologic phenomena Biology DC precursor lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Immune system Immunity vaccine cancer Progenitor cell Dendritic cell lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Acquired immune system Cell biology 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cord blood cord blood Stem cell Ex vivo |
Zdroj: | Cancers Volume 11 Issue 2 Cancers, Vol 11, Iss 2, p 181 (2019) |
ISSN: | 2072-6694 |
Popis: | 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 naï ve 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. |
Databáze: | OpenAIRE |
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