IL-33 blockade suppresses tumor growth of human lung cancer through direct and indirect pathways in a preclinical model
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Kailing Wang1,*, Shan Shan1,3,*, Zongjun Yang2, Xia Gu1, Yuanyuan Wang1, Chunhong Wang1 and Tao Ren1,3
1Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
2Department of Clinical Laboratory, Qingdao Women & Children Hospital, Qingdao 266034, China
3Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
*These authors have contributed equally to this work
Tao Ren, email: firstname.lastname@example.org
Chunhong Wang, email: email@example.com
Keywords: lung cancer, IL-33, tumor-associated macrophage, regulatory T cell
Abbreviations: NSCLC: non-small-cell lung cancer; TAM: tumor-associated macrophage; Treg: regulatory T cell
Received: February 18, 2017 Accepted: June 18, 2017 Published: August 02, 2017
Non-small-cell lung cancer (NSCLC) is the most common type in lung cancer, a leading cause of cancer-related death worldwide. Our previous study unraveled a pro-cancer function of IL-33 in fueling outgrowth and metastasis of human NSCLC cells. Herein, we determined that interfere with IL-33 activity was an effective strategy for limiting NSCLC tumor growth using a preclinical model with human NSCLC xenografts. IL-33 blockade efficiently inhibited tumor growth of NSCLC xenografts in immune-deficient mice. Mechanistically, IL-33 blockade suppressed outgrowth capacity of human NSCLC cells. Meanwhile, IL-33 blockade abrogated polarization of M2 tumor-associated macrophages (TAMs) and reduced accumulation of regulatory T cells (Tregs) in tumor microenvironments, shaping functional immune surveillance. In NSCLC patients, IL-33 expressions were positively correlated with Ki-67 proliferation index and expressions of M2 TAM- and Teg-related genes. These findings identify IL-33 as a dual-functional factor in NSCLC pathogenesis and suggest IL-33 blockade as a promising therapeutic for NSCLC patients.
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