DNT cell inhibits the growth of pancreatic carcinoma via NKG2D and MICA pathway in vivo

Objective To investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class Ⅰ chain-related molecules A(MICA) on DNT cell killing pancreatic carcinoma. Methods Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice, and then mice were randomly divided mice into 3 groups, blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. After 40 days mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. Results The blank group tumor volume and weight of blank group were significantly larger than those of gemcitabine group and DNT group (858.7±35.7 mg, 251.1±19.7 mg, 278.5±17.3 mg, P<0.001), but there were no significantly difference between DNT group and gemcitabine group. The tumor inhibition rate of gemcitabine and DNT cell were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than those in DNT group (P=0.001, P=0.003). NKG2D mRNA and protein levels in blank group were significantly lower than those in DNT cells group (P<0.001, P=0.001). Conclusion DNT cell can significantly inhibit the growth of pancreatic carcinoma in vivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D. Key words: DNT cell; Pancreatic carcinoma; NKG2D; MICA