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

Findlay, E. G. et al. (2019) Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy. OncoImmunology, 8(8), 1608106. (doi: 10.1080/2162402X.2019.1608106) (PMID:31413918) (PMCID:PMC6682359)

Abstract

Immunization of patients with autologous, 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 and . 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.

• Item Type: Articles
• Additional Information: This work was supported by the Royal Society [grant number DH150175] and Medical Research Council [grant number G1002046], [grant number G0802069].
• Keywords: CD103, CD141, CD86, CLEC9A, immunotherapy, PD1, cancer, cathelicidin, cross-presentation, dendritic cells, host defense peptide.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Finlayson, Mrs Lisa and Milling, Professor Simon
• Authors: Findlay, E. G., Currie, A. J., Zhang, A., Ovciarikova, J., Young, L., Stevens, H., McHugh, B. J., Canel, M., Gray, M., Milling, S. W.F., Campbell, J. D.M., Savill, J., Serrels, A., and Davidson, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: OncoImmunology
• Publisher: Taylor and Francis
• ISSN: 2162-4011
• ISSN (Online): 2162-402X
• Published Online: 01 May 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in OncoImmunology 8(8):1608106
• Publisher Policy: Reproduced under a Creative Commons License