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Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Artemisinin sensitizes tumor cells to NK cell-mediated cytolysis
Zhen Lu1, Jiacheng Bi1, Xiaochun Wan1
1Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China.
Abstract:
The antimalarial drug Artemisinin has been reported to possess direct anti-tumor effects on various types of tumor cells. However, its anti-tumor potential has not been fully revealed, and its effects on tumor susceptibility to immune surveillance by the host are still unknown. Natural killer (NK) cells are the first line in tumor surveillance by the host, and have been recognized as a promising target for tumor immunotherapy. Here, we reported that Artemisinin sensitized tumor cells to NK cell cytolysis. Both human K562 and Raji tumor cells, and mouse YAC-1 tumor cells were more susceptible to human or mouse NK cell cytolysis in vitro after Artemisinin pretreatment. Conjugation formation between tumor cells and NK cells was increased after pretreatment with Artemisinin. Such effects on tumor cells by Artemisinin might not be the results of tumor recognition by NK cells, since major ligands of NK cell surface receptors were not affected. Mechanistically, although Artemisinin didn't induce tumor cell apoptosis, Artemisinin enriched apoptosis-related gene sets in these tumor cells, which might predispose tumor cells to apoptosis upon NK cell cytolysis. Moreover, NK cell numbers, percentages, maturation and functions were preserved in the presence of Artemisinin in vitro, suggesting that Artemisinin displays detrimental effects only on tumor cells but not on immune cells. These data reveal a novel anti-tumor mechanism of Artemisinin and demonstrate that Artemisinin could be a promising drug candidate for cancer treatment.
Insights
Artemisinin, an antimalarial drug, enhances tumor cell susceptibility to natural killer (NK) cell attacks. This study reveals Artemisinin
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Artemisinin, an antimalarial, shows direct anti-tumor effects.
- Its impact on immune surveillance and natural killer (NK) cell activity is largely unknown.
- NK cells are crucial for host tumor surveillance and immunotherapy targets.
Purpose of the Study:
- To investigate Artemisinin's effect on tumor cell susceptibility to NK cell-mediated killing.
- To elucidate the underlying mechanisms of Artemisinin's anti-tumor activity.
- To assess Artemisinin's impact on NK cell function.
Main Methods:
- Pretreatment of human (K562, Raji) and mouse (YAC-1) tumor cells with Artemisinin.
- Assessment of NK cell-mediated tumor cell lysis in vitro.
- Analysis of tumor-NK cell conjugation and NK cell surface receptor ligands.
- Evaluation of apoptosis-related gene expression in tumor cells.
- Examination of NK cell numbers, maturation, and functions in the presence of Artemisinin.
Main Results:
- Artemisinin pretreatment sensitized various tumor cells to NK cell lysis.
- Increased conjugation between tumor cells and NK cells was observed.
- Artemisinin enriched apoptosis-related gene sets in tumor cells, predisposing them to apoptosis.
- NK cell numbers, maturation, and functions remained unaffected by Artemisinin.
- Artemisinin demonstrated selective toxicity towards tumor cells, not immune cells.
Conclusions:
- Artemisinin sensitizes tumor cells to NK cell-mediated killing, revealing a novel anti-tumor mechanism.
- Artemisinin may enhance anti-tumor immunity by making cancer cells more vulnerable to immune surveillance.
- Artemisinin is a potential candidate for cancer treatment, particularly in combination with immunotherapies.
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