Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 8, Issue -, Pages 1527-1538Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S66302
Keywords
tumor-associated macrophages; M1 macrophages; M2 macrophages; lung cancer; interferon-gamma; celecoxib
Categories
Funding
- National Natural Science Foundation of China [NSFC 81172236, NSFC 81372505]
- Key Science and Technology Program of Sichuan Province, People's Republic of China [2009SZ0152, 2011SZ0111]
- National Institute of General Medical Sciences [P20GM103518]
- National Cancer Institute of the National Institutes of Health [R01CA174714]
- Department of Defense Health Program through the Prostate Cancer Research Program [W81XWH-14-1-0050, W81XWH-14-1-0149, PC130118]
- Developmental Fund of Tulane Cancer Center (TCC)
- Louisiana Cancer Research Consortium (LCRC) Fund
- NATIONAL CANCER INSTITUTE [R01CA174714] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR020152] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103518] Funding Source: NIH RePORTER
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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 IFN gamma and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFN gamma 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 IFN gamma alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFN gamma and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFN gamma 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 IFN gamma and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFN gamma and celecoxib have potential to be further optimized into a new anticancer therapy.
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