Role Of Double Negative T Cells In The Treatment Of Pancreatic Cancer And The Underlying Mechanism

Objective This study aimed to explore double-negative T(DNT)cell cytotoxicity to pancreatic cancer and the effect of the Fas(CD95,APO-1)/Fas L(CD178)signaling pathway on this process.The expression of Fas receptor in human pancreatic cancer tissues was examined,and the clinical possibility of application of DNT cell immunotherapy was evaluated.Methods DNT cells from the peripheral blood of healthy volunteers were expanded in vitro.The inhibitory effect of DNT cells on pancreatic cancer cells was investigated using a CCK-8 assay and nude mouse tumor model.A mechanistic study was performed using pathway blocking assays.Expression of Fas in pancreatic cancer tissues was detected by immunohistochemistry.And analyze its correlation with clinicopathological features.Results DNT cells were amplified in vitro with > 90% purity,and the growth of pancreatic cancer in vitro was significantly inhibited by DNT cells(P<0.001).After coculture with DNT cells,Fas,caspase-8,cleaved caspase-8 and cleaved caspase-3 showed increased expression in pancreatic cancer cells.When blocking agent decoy receptor 3(Dc R3)was added,the antitumor effect of DNT cells and the expression of Fas,caspase-8,cleaved caspase-8 and cleaved caspase-3 were reduced in pancreatic cancer cells.In the nude mouse tumor model,the tumor volume and weight were lower in the DNT cell group and gemcitabine group than in the blank control group.Additionally,the expression of Fas,caspase-8 and cleaved caspase-8 was higher in the DNT cell group and gemcitabine group than in the blank control group.Fas expression was significantly higher in cancer tissues than in adjacent normal tissues(P=0.003).And has correlation with tumor differentiation and nerve infiltration(P=0.017,P=0.012).Conclusion DNT cells inhibited the growth of pancreatic cancer,and the Fas/Fas L signaling pathway was involved in this process.Compared with peritumoral tissues,Fas expression is decreased in pancreatic cancer tissues and is associated with tumor differentiation and neural invasion.