期刊
FASEB JOURNAL
卷 33, 期 12, 页码 13254-13266出版社
WILEY
DOI: 10.1096/fj.201900799RR
关键词
mechanical force; macrophage polarization; cancer; immunotherapy; focal adhesion kinase
资金
- National Natural Science Foundation of China [81601698, 81601688, 81620108019, 81830078]
Macrophages (M phi s) can be used as a part of cell-based cancer immunotherapy. However, they may be hampered by a failure to effectively and stably regulate their polarization state to enhance their tumoricidal effects. In this work, mechanical stretch (MS), as a biology-free modulatory method, was shown to enhance M1 polarization and tumoricidal effects. By using an in vitro Flexcell Tension system, we found that murine M phi RAW264.7 cells showed higher M1 polarization related mRNA expression and cytokine release after MS. Further molecular analyses found that focal adhesion kinase and NF-kappa B activation occurred in the MS-induced M1 polarization. Coculture of MS-preconditioned M phi with B16F10 skin melanoma cells in vitro showed that the proliferation of B16F10 cells decreased, whereas caspase-3 induced apoptosis increased. Importantly, the injection of MS-preconditioned M phi into murine skin melanomas in vivo impeded tumor growth; lesions were characterized by increased amounts of M1 M phi, decreased tumor cell proliferation, and increased tumor cell apoptosis in the tumor microenvironment. Together, our results suggest that MS could be used as a simple preconditioning approach to prepare tumoricidal M1 M phi for cancer immunotherapy.
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