Browsing by Author "Chang, Cheng-Yen"

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    Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
    (AAAS, 2022) Chang, Cheng-Yen; You, Ran; Armstrong, Dominique; Bandi, Ashwini; Cheng, Yi-Ting; Burkhardt, Philip M.; Becerra-Dominguez, Luis; Madison, Matthew C.; Tung, Hui-Ying; Zeng, Zhimin; Wu, Yifan; Song, Lizhen; Phillips, Patricia E.; Porter, Paul; Knight, John M.; Putluri, Nagireddy; Yuan, Xiaoyi; Marcano, Daniela C.; McHugh, Emily A.; Tour, James M.; Catic, Andre; Maneix, Laure; Burt, Bryan M.; Lee, Hyun-Sung; Corry, David B.; Kheradmand, Farrah
    Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A–dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non–small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.