miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvir...

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Bibliographic Details
Published in:Cancers 2021-12, Vol.13 (24), p.6252
Main Authors: Chang, Wei-An, Tsai, Ming-Ju, Hung, Jen-Yu, Wu, Kuan-Li, Tsai, Ying-Ming, Huang, Yung-Chi, Chang, Chao-Yuan, Tsai, Pei-Hsun, Hsu, Ya-Ling
Format: Article
Language:English
Subjects:
Angiogenesis
Animal models
Antibodies
Antigens
Apoptosis
Cancer therapies
Cell growth
Cytotoxicity
Effector cells
Extracellular vesicles
Flow cytometry
Hypoxia
Inflammation
Lung cancer
Metastases
MicroRNAs
Natural killer cells
Phenotypes
Physiology
Tumor microenvironment
Tumorigenesis
Tumors
Vascular endothelial growth factor
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Summary:Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13246252