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Gentschev, I.* ; Petrov, I.* ; Ye, M.* ; Kafuri Cifuentes, L.* ; Toews, R.* ; Cecil, A. ; Oelschaeger, T.A.* ; Szalay, A.A.*

Tumor colonization and therapy by Escherichia coli nissle 1917 strain in syngeneic tumor-bearing mice is strongly affected by the gut microbiome.

Cancers 14:6033 (2022)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
In the past, different bacterial species have been tested for cancer therapy in preclinical and clinical studies. The success of bacterial cancer therapy is mainly dependent on the ability of the utilized bacteria to overcome the host immune defense system to colonize the tumors and to initiate tumor-specific immunity. In recent years, several groups have demonstrated that the gut microbiome plays an important role of modulation of the host immune response and has an impact on therapeutic responses in murine models and in cohorts of human cancer patients. Here we analyzed the impact of the gut microbiome on tumor colonization and tumor therapy by the Escherichia coli Nissle 1917 (EcN) strain. This EcN strain is a promising cancer therapy candidate with probiotic properties. In our study, we observed significantly better tumor colonization by EcN after antibiotic-induced temporal depletion of the gut microbiome and after two intranasal applications of the EcN derivate (EcN/pMUT-gfp Knr) in 4T1 tumor-bearing syngeneic BALB/c mice. In addition, we demonstrated significant reduction in tumor growth and extended survival of the EcN-treated mice in contrast to phosphate-buffered saline (PBS)-treated tumor-bearing control animals. Multispectral imaging of immune cells revealed that depletion of the gut microbiome led to significantly lower infiltration of cytotoxic and helper T cells (CD4 and CD8 cells) in PBS tumors of mice pretreated with antibiotics in comparison with antibiotic untreated PBS—or EcN treated mice. These findings may help in the future advancement of cancer treatment strategies using E. coli Nissle 1917.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bacterial Cancer Therapy ; E. Coli Nissle 1917 ; Gut Microbiome ; Probiotic Bacterium ; Syngeneic Tumor-bearing Mice ; Tumor ; Tumor Colonization; Enzyme-prodrug Therapy; Breast-tumors; Cancer; Bacteria; Immunity; Cells; Expression; Growth
ISSN (print) / ISBN 2072-6694
Zeitschrift Cancers
Quellenangaben Band: 14, Heft: 24, Seiten: , Artikelnummer: 6033 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Molekulare Endokrinologie und Metabolismus (MEM)
Förderungen Julius-Maximilians-Universität Würzburg
Hope Realized Medical Foundation