Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model

Johnson, S. A. et al. (2021) Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model. European Journal of Immunology, (doi: 10.1002/eji.202048913) (PMID:34633664) (Early Online Publication)

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Abstract

The use of bacteria as an alternative cancer therapy has been reinvestigated in recent years. SL7207: an auxotrophic Salmonella enterica serovar Typhimurium aroA mutant with immune-stimulatory potential has proven a promising strain for this purpose. Here, we show that systemic administration of SL7207 induces melanoma tumor growth arrest in vivo, with greater survival of the SL7207-treated group compared to control PBS-treated mice. Administration of SL7207 is accompanied by a change in the immune phenotype of the tumor-infiltrating cells toward pro-inflammatory, with expression of the TH1 cytokines IFN-γ, TNF-α, and IL-12 significantly increased. Interestingly, Ly6C+MHCII+ monocytes were recruited to the tumors following SL7207 treatment and were pro-inflammatory. Accordingly, the abrogation of these infiltrating monocytes using clodronate liposomes prevented SL7207-induced tumor growth inhibition. These data demonstrate a previously unappreciated role for infiltrating inflammatory monocytes underlying bacterial-mediated tumor growth inhibition. This information highlights a possible novel role for monocytes in controlling tumor growth, contributing to our understanding of the immune responses required for successful immunotherapy of cancer.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:McIntosh, Ms Anne and Blyth, Professor Karen and HULME, Heather and Bravo-Blas, Dr Alberto and Tait, Professor Stephen and Ormsby, Dr Michael and Wall, Dr Daniel and Milling, Professor Simon and Coffelt, Dr Seth and Mowat, Professor Allan and Mason, Miss Susan and Johnson, Síle and Wessel, Miss Hannah
Authors: Johnson, S. A., Ormsby, M. J., Wessel, H., Hulme, H., Bravo-Blas, A., McIntosh, A., Mason, S., Coffelt, S., Tait, S. W.G., Mcl. Mowat, A., Milling, S., Blyth, K., and Wall, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:11 October 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Journal of Immunology 2021
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
168481Molecular Functions in Disease PhD Studentship (2013-2017)Darren MoncktonWellcome Trust (WELLCOTR)102460/Z/13/ZMCSB - Molecular Genetics
167488Survival and dissemination of enteric pathogens through exploitation and inhibition of programmed cell death pathways in circulating immune cells.Daniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/K008005/1III - Bacteriology
173261Propionic acid use in agriculture and food production is driving evolution of novel Escherichia coli pathotypesDaniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/P003281/1III - Bacteriology