Cigarette smoke sustains immunosuppressive microenvironment inducing M2 macrophage polarization and viability in lung cancer settings.

Autor: Bianchi F; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.; U.O. Laboratorio di Morfologia Umana Applicata, IRCCS San Donato, Milan, Italy., Le Noci V; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy., Bernardo G; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy., Gagliano N; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy., Colombo G; Department of Biosciences, University of Milan, Milan, Italy., Sommariva M; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.; Unit of Microenvironment and Biomarkers of Solid Tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Palazzo M; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Dalle-Donne I; Department of Biosciences, University of Milan, Milan, Italy., Milzani A; Department of Biosciences, University of Milan, Milan, Italy., Pupa S; Unit of Microenvironment and Biomarkers of Solid Tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Tagliabue E; Unit of Microenvironment and Biomarkers of Solid Tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Sfondrini L; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.; Unit of Microenvironment and Biomarkers of Solid Tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 May 22; Vol. 19 (5), pp. e0303875. Date of Electronic Publication: 2024 May 22 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0303875
Abstrakt: Background: It is amply demonstrated that cigarette smoke (CS) has a high impact on lung tumor progression worsening lung cancer patient prognosis and response to therapies. Alteration of immune cell types and functions in smokers' lungs have been strictly related with smoke detrimental effects. However, the role of CS in dictating an inflammatory or immunosuppressive lung microenvironment still needs to be elucidated. Here, we investigated the effect of in vitro exposure to cigarette smoke extract (CSE) focusing on macrophages.
Methods: Immortalized murine macrophages RAW 264.7 cells were cultured in the presence of CS extract and their polarization has been assessed by Real-time PCR and cytofluorimetric analysis, viability has been assessed by SRB assay and 3D-cultures and activation by exposure to Poly(I:C). Moreover, interaction with Lewis lung carcinoma (LLC1) murine cell models in the presence of CS extract were analyzed by confocal microscopy.
Results: Obtained results indicate that CS induces macrophages polarization towards the M2 phenotype and M2-phenotype macrophages are resistant to the CS toxic activity. Moreover, CS impairs TLR3-mediated M2-M1 phenotype shift thus contributing to the M2 enrichment in lung smokers.
Conclusions: These findings indicate that, in lung cancer microenvironment of smokers, CS can contribute to the M2-phenotype macrophages prevalence by different mechanisms, ultimately, driving an anti-inflammatory, likely immunosuppressive, microenvironment in lung cancer smokers.
Competing Interests: the authors have declared that no competing interests exist.
(Copyright: © 2024 Bianchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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