Increased expression of SLC38A2 in natural killer cells promotes anti-tumor immunity / 肿瘤

ABSTRACT

Objective:To investigate the effect of solute carrier family 38 member 2(SLC38A2)on the cytotoxicity of natural killer(NK)cells against tumor cells. Methods:Real-time fluorescence quantitative PCR was used to detect the mRNA expression of different glutamine transporters(SLC38A2,SLC1A5,SLC7A5,SLC7A1 and SLC1A4)in natural killer(NK)cells under glutamine deficiency or the spleens of dieting mice.NK-92MI cells were infected with the recombinant lentivirus carrying SLC38A2 gene to construct SLC38A2-overexpressing NK cells.After SLC38A2 overexpression or increasing glutamine concentration,the lactate dehydrogenase releasing assay was used to detect the cytotoxicity of NK cells against pancreatic tumor cell PANC-1 and liver cancer cell HUH-7,and the apoptosis of two tumor cells was detected by flow cytometry assay after AnnexinV/7-AAD staining.Finally,the expression level of cell surface CD107a,a degranulation marker,as well as the expression of cytotoxic effectors interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α),in NK cells was further investigated by flow cytometry. Results:The mRNA expression of glutamine transporter SLC38A2 was significantly upregulated in NK cells under glutamine deficient conditions and the spleens of dieting mice(P＜0.001,P＜0.01).SLC38A2-overexpressing NK-92MI cell model were successfully established.Overe-xpression of SLC38A2 or glutamine treatment could significantly increase the cytotoxicity of NK-92MI cells against pancreatic tumor cell PANC-1 and liver cancer cell HUH-7(P＜0.05)and obviously promote the apoptosis of tumor cells(P＜0.01).Flow cytometry analysis results showed that SLC38A2-overexpressing NK-92MI cells significantly increased CD1 07a expression on the cell surface and produced more IFN-γ and TNF-α when co-cultured with tumor cells(P＜0.001). Conclusion:The amino acid transporter SLC38A2 can significantly enhance the cytotoxicity of NK cells against tumor cells.