Live or Heat-Killed <i>Lactobacillus rhamnosus</i> Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model

oleh: Valentino Le Noci, Giancarla Bernardo, Giacomo Manenti, Gabriele Infante, Dariush Khaleghi Hashemian, Lucia Minoli, Simone Canesi, Francesca Bianchi, Tiziana Triulzi, Stefania Arioli, Loris De Cecco, Simone Guglielmetti, Federico Ambrogi, Camilla Recordati, Nicoletta Gagliano, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini

Format: Article
Diterbitkan: MDPI AG 2022-10-01

Deskripsi

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead <i>L. rhamnosus GG</i> (<i>L.RGG</i>)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed <i>L.RGG</i>, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both <i>L.RGG</i> and V/N reduced Tregs in the lung. In <i>L.RGG</i>-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights <i>L.RGG</i> aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.