Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy

E.G. Findlay; A.J. Currie; A. Zhang; J. Ovciarikova; L. Young; H. Stevens; B.J. McHugh; M. Canel; M. Gray; S.W.F. Milling; J.D.M. Campbell; J. Savill; A. Serrels; D.J. Davidson

doi:10.1080/2162402X.2019.1608106

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Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy

Journal article

Open access

Peer reviewed

Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy

E.G. Findlay, A.J. Currie, A. Zhang, J. Ovciarikova, L. Young, H. Stevens, B.J. McHugh, M. Canel, M. Gray, S.W.F. Milling, …

OncoImmunology, Vol.8(8)

2019

DOI: https://doi.org/10.1080/2162402X.2019.1608106

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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 Research
A.J. Currie (Author/Creator) - Murdoch University
A. Zhang (Author/Creator) - Centre for Inflammation Research
J. Ovciarikova (Author/Creator) - Centre for Inflammation Research
L. Young (Author/Creator) - Centre for Inflammation Research
H. Stevens (Author/Creator) - Centre for Inflammation Research
B.J. McHugh (Author/Creator) - Centre for Inflammation Research
M. Canel (Author/Creator) - Centre for Inflammation Research
M. Gray (Author/Creator) - Centre for Inflammation Research
S.W.F. Milling (Author/Creator)
J.D.M. Campbell (Author/Creator)
J. Savill (Author/Creator) - Centre for Inflammation Research
A. Serrels (Author/Creator) - Centre for Inflammation Research
D.J. Davidson (Author/Creator) - Murdoch University
Publication Details: OncoImmunology, Vol.8(8)
Publisher: Taylor & Francis
Identifiers: 991005540822907891
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