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, 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
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.
Keywords: aerosolization; antibiotics; cancer immunosurveillance; immunosuppression and/or suppressor cells; lung microbiota; mouse models; probiotics.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed