PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis

Liwen Li; Fan Sun; Lei Han; Xujie Liu; Yadong Xiao; Alyssa D. Gregory; Steven D. Shapiro; Gutian Xiao; Zhaoxia Qu

doi:10.1172/jci.insight.144394

Published February 4, 2021 - More info

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Abstract

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.

PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis

Liwen Li,¹ Fan Sun,¹ Lei Han,¹ Xujie Liu,¹ Yadong Xiao,² Alyssa D. Gregory,² Steven D. Shapiro,² Gutian Xiao,¹ and Zhaoxia Qu¹

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PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis

Liwen Li,1 Fan Sun,1 Lei Han,1 Xujie Liu,1 Yadong Xiao,2 Alyssa D. Gregory,2 Steven D. Shapiro,2 Gutian Xiao,1 and Zhaoxia Qu1

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Liwen Li,¹ Fan Sun,¹ Lei Han,¹ Xujie Liu,¹ Yadong Xiao,² Alyssa D. Gregory,² Steven D. Shapiro,² Gutian Xiao,¹ and Zhaoxia Qu¹