Journal article
Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy
OncoImmunology, Vol.8(8)
2019
Abstract
Immunization of patients with autologous, ex vivo matured dendritic cell (DC) preparations, in order to prime antitumor T-cell responses, is the focus of intense research. Despite progress and approval of clinical approaches, significant enhancement of these personalized immunotherapies is urgently needed to improve efficacy. We show that immunotherapeutic murine and human DC, generated in the presence of the antimicrobial host defense peptide LL-37, have dramatically enhanced expansion and differentiation of cells with key features of the critical CD103 + /CD141 + DC subsets, including enhanced cross-presentation and co-stimulatory capacity, and upregulation of CCR7 with improved migratory capacity. These LL-37-DC enhanced proliferation, activation and cytokine production by CD8 + (but not CD4 + ) T cells in vitro and in vivo. Critically, tumor antigen-presenting LL-37-DC increased migration of primed, activated CD8 + T cells into established squamous cell carcinomas in mice, and resulted in tumor regression. This advance therefore has the potential to dramatically enhance DC immunotherapy protocols.
Details
- Title
- Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy
- Authors/Creators
- E.G. Findlay (Author/Creator) - Centre for Inflammation ResearchA.J. Currie (Author/Creator) - Murdoch UniversityA. Zhang (Author/Creator) - Centre for Inflammation ResearchJ. Ovciarikova (Author/Creator) - Centre for Inflammation ResearchL. Young (Author/Creator) - Centre for Inflammation ResearchH. Stevens (Author/Creator) - Centre for Inflammation ResearchB.J. McHugh (Author/Creator) - Centre for Inflammation ResearchM. Canel (Author/Creator) - Centre for Inflammation ResearchM. Gray (Author/Creator) - Centre for Inflammation ResearchS.W.F. Milling (Author/Creator)J.D.M. Campbell (Author/Creator)J. Savill (Author/Creator) - Centre for Inflammation ResearchA. Serrels (Author/Creator) - Centre for Inflammation ResearchD.J. Davidson (Author/Creator) - Murdoch University
- Publication Details
- OncoImmunology, Vol.8(8)
- Publisher
- Taylor & Francis
- Identifiers
- 991005540822907891
- Copyright
- © 2019 The Author(s)
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.358 Dendritic Cell Therapy
- Web Of Science research areas
- Immunology
- Oncology
- ESI research areas
- Biology & Biochemistry