摘要
Background:Human natural killer(NK)cells have attracted widespread attention as a potential adoptive cell therapy(ACT).However,the therapeutic effects of NK cell infusion in patients with solid tumors are limited.There is an urgent need to explore a suitable new treatment plan to overcome weaknesses and support the superior therapeutic activity of NK cells.Methods:In this study,the mechanisms underlying the susceptibility of gastric cancer(GC)cell lines AGS,HGC-27,and NCI-N87 to NK cell-mediated cytotoxicity were explored.Results:Lactic dehydrogenase(LDH)release assays showed that all three GC cell lines were susceptible to the umbilical cord blood NK(UCB-NK)cells,and HGC-27 cells with high CD56 expression were the most sensitive to UCB-NK,followed by NCI-N87 and AGS.When the expression of CD56 in HGC-27 cells decreased,the lytic activity of NK cells in HGC-27 cells was abating.In addition,combining oxaliplatin with NK cells produced additive anti-tumor effects in vitro,which may have resulted from oxaliplatin-induced NK group 2 member D(NKG2DL)upregulation in GC cells.These results of cytotoxicity activity showed that inhibition of CD56 expression might suppress the sensitivity of GC cells to NK cell-mediated cytotoxicity,and upregulation of the expression of NKG2DL on the surface of GC cells by oxaliplatin could enhance the killing sensitivity of NK cells.Conclusion:Collectively,our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC.
基金
supported by the CAMS Innovation Fund for Medical Sciences(Grants:2021-I2M-1-070)
National Natural Science Foundation of China(Grants 82373767).
