title: Interferon-γ and celecoxib inhibit lung-tumor growth through modulating M2/M1 macrophage ratio in the tumor microenvironment.
abstract: Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFNγ and celecoxib have potential to be further optimized into a new anticancer therapy.
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Mei
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pu
authors.affiliation: Department of Structural and Cellular Biology, New Orleans, LA, USA ; Department of Orthopaedic Surgery, New Orleans, LA, USA ; Tulane Cancer Center, New Orleans, LA, USA ; Louisiana Cancer Research Consortium, New Orleans, LA, USA ; Tulane Center for Stem Cell Research and Regenerative Medicine, New Orleans, LA, USA ; Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Zongbing
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Thoracic Surgery, West China Hospital, People's Republic of China ; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, People's Republic of China.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007371:Interferon-gamma / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D007371:Interferon-gamma; D000068579:Celecoxib
keywords: M1 macrophages; M2 macrophages; celecoxib; interferon-γ; lung cancer; tumor-associated macrophages