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

Author:

Bianchi FrancescaORCID,Le Noci Valentino,Bernardo Giancarla,Gagliano Nicoletta,Colombo Graziano,Sommariva Michele,Palazzo Michele,Dalle-Donne Isabella,Milzani Aldo,Pupa Serenella,Tagliabue Elda,Sfondrini LuciaORCID

Abstract

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.

Funder

Associazione Italiana per la Ricerca sul Cancro

Fondazione Umberto Veronesi

Università degli Studi di Milano

Publisher

Public Library of Science (PLoS)

Reference85 articles.

1. Prevention and Early Detection for NSCLC: Advances in Thoracic Oncology 2018;H. Balata;J. Thorac. Oncol,2019

2. The state of molecular biomarkers for the early detection of lung cancer;M. Hassanein;Cancer Prev. Res. (Phila),2012

3. Treatment of non-small cell lung cancer (NSCLC);K. Zarogoulidis;J. Thorac. Dis,2013

4. Genetic susceptibility to lung cancer—light at the end of the tunnel?;A.L. Marshall;Carcinogenesis,2013

5. Cigarette smoke induces DNA damage and alters base-excision repair and tau levels in the brain of neonatal mice;S. La Maestra;Toxicol. Sci,2011

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