Natural killer cell exhaustion in lung cancer.

ABSTRACT

OBJECTIVES: Lung cancer is one of the most frequently diagnosed cancers worldwide. However, the potential causes of lung cancer oncogenesis are still unclear. This study aims to explore the phenomenon and mechanism of NK cell exhaustion in lung cancer and lay the foundation for developing a targeting strategy to ameliorate immune cell exhaustion in cancer. MATERIALS AND METHODS: NK cells were isolated from the blood samples of lung cancer patients and healthy volunteers. After culture in vitro, the colony forming ability, cytotoxicity, apoptosis and receptor expression of NK cells in the peripheral blood from the lung cancer patients and the volunteers were analyzed by flow cytometry and the corresponding methods. The correlation between the NK cell profile and lung cancer occurrence was analyzed as well. RESULTS: The colony formation and cytotoxicity of the NK cells from the lung cancer group were significantly decreased compared to whose of the NK cells from volunteers. The expression of NKG2A was upregulated and CD226 was downregulated significantly in the lung cancer group compared with the control group. Furthermore, through correlation analysis, the colony forming level, cytotoxicity and CD226 expression level were significantly negatively correlated with lung cancer, and the expression level of NKG2A was significantly positively correlated with lung cancer. Moreover, the impaired colony formation of NK cells was significantly correlated with NK cell functional exhaustion in lung cancer. CONCLUSIONS: The downregulated CD226 expression and the upregulated NKG2A expression may serve as potential markers of NK cells exhaustion in lung cancer.