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Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2018 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 7, no 3, article id e1395126Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.

Place, publisher, year, edition, pages
2018. Vol. 7, no 3, article id e1395126
Keywords [en]
Allogeneic dendritic cells, cell-based immunotherapy, innate immune cells, cell activation
National Category
Immunology in the medical area Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-346363DOI: 10.1080/2162402X.2017.1395126ISI: 000423567000006OAI: oai:DiVA.org:uu-346363DiVA, id: diva2:1191166
Funder
Swedish Cancer Society, CAN 2013/373; CAN 2016/318Swedish Childhood Cancer Foundation, PR2015-0049Swedish Research Council, 2015-03688Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-16Bibliographically approved

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Fotaki, GrammatikiJin, ChuanRamachandran, MohanrajKerzeli, Iliana KyriakiKarlsson-Parra, AlexYu, DiEssand, Magnus

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Fotaki, GrammatikiJin, ChuanRamachandran, MohanrajKerzeli, Iliana KyriakiKarlsson-Parra, AlexYu, DiEssand, Magnus
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Oncoimmunology
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