Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy: A Strategy to Promote Immunosurveillance against Lung Metastases

Valentino Le Noci, Simone Guglielmetti, Stefania Arioli, Chiara Camisaschi, Francesca Bianchi, Michele Sommariva, Chiara Storti, Tiziana Triulzi, Chiara Castelli, Andrea Balsari, Elda Tagliabue, Lucia Sfondrini

Research output: Contribution to journalArticle

Abstract

Pulmonary immunological tolerance to inhaled particulates might create a permissive milieu for lung metastasis. Lung microbiota contribute to pulmonary tolerance; here, we explored whether its manipulation via antibiotic or probiotic aerosolization favors immune response against melanoma metastasis. In lungs of vancomycin/neomycin-aerosolized mice, a decrease in bacterial load was associated with reduced regulatory T cells and enhanced T cell and NK cell activation that paralleled a significant reduction of melanoma B16 lung metastases. Reduction of metastases also occurred in lungs transplanted with bacterial isolates from antibiotic-treated lungs. Aerosolized Lactobacillus rhamnosus strongly promoted immunity against B16 lung metastases as well. Furthermore, probiotics or antibiotics improved chemotherapy activity against advanced B16 metastases. Thus, we identify a role for lung microbiota in metastasis and show that its targeting via aerosolization is a therapy that can prevent metastases and enhance responses to chemotherapy.

Original languageEnglish
Pages (from-to)3528-3538
Number of pages11
JournalCell Reports
Volume24
Issue number13
DOIs
Publication statusPublished - Sep 25 2018

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Immunologic Monitoring
Microbiota
Probiotics
Aerosols
Chemotherapy
T-cells
Modulation
Neoplasm Metastasis
Anti-Bacterial Agents
Lung
Neomycin
Vancomycin
Therapeutics
Chemical activation
Lactobacillus rhamnosus
Drug Therapy
Experimental Melanomas
Bacterial Load
Regulatory T-Lymphocytes
Natural Killer Cells

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Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy : A Strategy to Promote Immunosurveillance against Lung Metastases. / Le Noci, Valentino; Guglielmetti, Simone; Arioli, Stefania; Camisaschi, Chiara; Bianchi, Francesca; Sommariva, Michele; Storti, Chiara; Triulzi, Tiziana; Castelli, Chiara; Balsari, Andrea; Tagliabue, Elda; Sfondrini, Lucia.

In: Cell Reports, Vol. 24, No. 13, 25.09.2018, p. 3528-3538.

Research output: Contribution to journalArticle

Le Noci, Valentino ; Guglielmetti, Simone ; Arioli, Stefania ; Camisaschi, Chiara ; Bianchi, Francesca ; Sommariva, Michele ; Storti, Chiara ; Triulzi, Tiziana ; Castelli, Chiara ; Balsari, Andrea ; Tagliabue, Elda ; Sfondrini, Lucia. / Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy : A Strategy to Promote Immunosurveillance against Lung Metastases. In: Cell Reports. 2018 ; Vol. 24, No. 13. pp. 3528-3538.
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abstract = "Pulmonary immunological tolerance to inhaled particulates might create a permissive milieu for lung metastasis. Lung microbiota contribute to pulmonary tolerance; here, we explored whether its manipulation via antibiotic or probiotic aerosolization favors immune response against melanoma metastasis. In lungs of vancomycin/neomycin-aerosolized mice, a decrease in bacterial load was associated with reduced regulatory T cells and enhanced T cell and NK cell activation that paralleled a significant reduction of melanoma B16 lung metastases. Reduction of metastases also occurred in lungs transplanted with bacterial isolates from antibiotic-treated lungs. Aerosolized Lactobacillus rhamnosus strongly promoted immunity against B16 lung metastases as well. Furthermore, probiotics or antibiotics improved chemotherapy activity against advanced B16 metastases. Thus, we identify a role for lung microbiota in metastasis and show that its targeting via aerosolization is a therapy that can prevent metastases and enhance responses to chemotherapy.",
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