ResearchIn-Press PreviewOncology
Open Access | 10.1172/jci.insight.144394
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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Li, L.
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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Han, L.
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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Gregory, A.
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
2Department of Medicine, University of Pittsburgh, Pittsburgh, United States of America
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Published February 4, 2021 - More info
One of the most fundamental and challenging questions in the cancer field is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the tumor suppressor PDZ-LIM domain-containing protein 2 (PDLIM2) as a checkpoint of alveolar macrophages (AMs) important for lung tumor suppression. During lung tumorigenesis, PDLIM2 expression in AMs is down-regulated by reactive oxygen species (ROS)-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 down-regulation leads to constitutive activation of the transcription factor signal transducer and activator of transcription 3 (STAT3), driving AM pro-tumorigenic polarization/activation and differentiation from monocytes attracted from the circulation to suppress cytotoxic T lymphocytes (CTLs) and promote lung cancer. PDLIM2 down-regulation also decreases AM phagocytosis. These findings establish ROS/BACH1/PDLIM2/STAT3 as a signaling pathway driving AMs for lung tumor promotion.