Abstract
Natural killer cells (NK cells) are important immune cells which have attracted increasing attention in cancer immunotherapy. Due to the heterogeneity of cells, individual cancer cells show different resistance to NK cytotoxicity, which has been revealed by flow cytometry. Here we used label-free mass cytometry (CyESI-MS) as a new tool to analyze the metabolites in Human Hepatocellular Carcinoma (HepG2) cells at the single-cell level after the interaction with different numbers of NK92 MI cells. A large amount of chemical information from individual HepG2 cells was obtained showing the process of cell apoptosis induced by NK cells. Nineteen metabolites which consecutively change during cell apoptosis were revealed by calculating their average relative intensity. Four metabolic pathways were impacted during cell apoptosis which hit 4 metabolites including glutathione (GSH), creatine, glutamic acid and taurine. We found that the HepG2 cells could be divided into two phenotypes after co-culturing with NK cells according to the bimodal distribution of concentration of these 4 metabolites. The correlation between metabolites and different apoptotic pathways in the early apoptosis cell group was established by the 4 metabolites at the single-cell level. This is a new idea of using single-cell specific metabolites to reveal the metabolic heterogeneity in cell apoptosis which would be a powerful means for evaluating the cytotoxicity of NK cells.
Highlights
The correlation between metabolites and different apoptotic pathways in the early apoptosis cell group was established by the 4 metabolites at the single-cell level
This is a new idea of using single-cell specific metabolites to reveal the metabolic heterogeneity in cell apoptosis which would be a powerful means for evaluating the cytotoxicity of NK cells
Because CyESI is considered as a so ion source, the cell-related MS pro le contains a variety of cellular small molecular metabolite information, such as protonated metabolite ions, which may be useful to reveal the process of apoptosis in cancer cells induced by NK cells
Summary
Natural killer cells (NK cells) are one of the most important immune cells in the human body, and are the initial immune component in the immune system to recognize and kill cancer cells.[1,2,3,4] Different from B lymphocytes and T lymphocytes, the immune reaction mediated by NK cells can directly cause cytotoxicity without the introduction of antigens, so NK cells have more comprehensive ability in cancer cell killing.[5,6] Up to now, the therapy of ampli cation and reinfusion of the heterogeneous NK cells has been successfully used to treat liver cancer,[7] rectal cancer,[8] breast cancer[9,10,11] and acute myeloid leukemia[12,13,14] in clinics. Dynamic metabolic change of cancer cells induced by natural killer cells at the single-cell level studied by label-free mass cytometry† Four metabolic pathways were impacted during cell apoptosis which hit 4 metabolites including glutathione (GSH), creatine, glutamic acid and taurine.
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