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

Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy
Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy
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
2162-402X
Gwyer Findlay, Emily
b6787bbb-66ad-435c-ad2c-c18ffaf6b7d8
Gwyer Findlay, Emily
b6787bbb-66ad-435c-ad2c-c18ffaf6b7d8

Gwyer Findlay, Emily (2019) Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy. OncoImmunology, 8 (8), [1608106]. (doi:10.1080/2162402x.2019.1608106).

Record type: Article

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

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Accepted/In Press date: 13 March 2019
Published date: 1 May 2019

Identifiers

Local EPrints ID: 471866
URI: http://eprints.soton.ac.uk/id/eprint/471866
ISSN: 2162-402X
PURE UUID: 92fad4b3-0bc9-4835-980a-73d35bc9290b
ORCID for Emily Gwyer Findlay: ORCID iD orcid.org/0000-0002-2311-6589

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Date deposited: 22 Nov 2022 17:30
Last modified: 17 Mar 2024 04:14

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Author: Emily Gwyer Findlay ORCID iD

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