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 L. rhamnosus GG (L.RGG)-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 L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-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 L.RGG 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.

Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model / V. Le Noci, G. Bernardo, G. Manenti, G. Infante, D. Khaleghi Hashemian, L. Minoli, S. Canesi, F. Bianchi, T. Triulzi, S. Arioli, L. De Cecco, S. Guglielmetti, F. Ambrogi, C. Recordati, N. Gagliano, E. Tagliabue, M. Sommariva, L. Sfondrini. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:21(2022 Oct 22), pp. 12748.1-12748.20. [10.3390/ijms232112748]

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

V. Le Noci
Primo
;
G. Bernardo
Secondo
;
G. Infante;D. Khaleghi Hashemian;L. Minoli;S. Canesi;F. Bianchi;S. Arioli;S. Guglielmetti;F. Ambrogi;C. Recordati;N. Gagliano;M. Sommariva
Penultimo
;
L. Sfondrini
Ultimo
2022

Abstract

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 L. rhamnosus GG (L.RGG)-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 L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-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 L.RGG 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.
IgA; J chain; Lactobacillus rhamnosus; aerosol; carcinogenesis; lung cancer; lung microbiota; mouse models; tumor prevention; urethane; Mice; Animals; Carcinogens; Hot Temperature; Disease Models, Animal; Tumor Microenvironment; Lactobacillus rhamnosus; Lung Neoplasms; Probiotics; Adenoma
Settore MED/04 - Patologia Generale
PRIN201719FAMBR_01 - Innovative statistical methods in biomedical research on biomarkers: from their identification to their use in clinical practice - AMBROGI, FEDERICO - PRIN2017 - PRIN bando 2017 - 2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/946461
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