Double-negative T Cells Inhibit Proliferation and Invasion of Human Pancreatic Cancer Cells in Co-culture

Abstract

Background/aim: Double-negative T (DNT) cells are phenotypically CD3⁺CD4^-CD8^-T cells. This study aimed to investigate the anti-cancer activity of DNT cells against pancreatic cancer cells.

Materials and methods: DNT cells were isolated from human peripheral blood. The effect of DNT cells on proliferation and invasion of the human pancreatic cell line Panc-1 was assessed. Expression of Nrf2 and Fas in Panc-1 cells co-cultured with DNT cells was analyzed with RT-PCR. The supernatants of Panc-1 and DNT co-cultures were analyzed with ELISA for IFN-r and FasL levels.

Results: The isolated DNT cell phenotype was CD4^-CD8^-CD56^- CD3⁺TCR (T cell receptor) α/β⁺ T cells with more than 90% purity. Panc-1 cell proliferation was significantly inhibited by co-culture with DNT cells. Panc-1 cells co-cultured with DNT cells showed significantly reduced cell invasion. Panc-1 cells co-cultured with DNT cells showed increased Nrf2 and Fas mRNA expression. Increased INF-r and FasL levels were detected in the supernatants of co-cultures of DNT and pancreatic cells.

Conclusion: DNT cells inhibited proliferation and invasion of human pancreatic cancer cells. The INF-r, Fas/FasL pathway and Nrf2 may be involved in the anti-cancer effect of DNT cells against human pancreatic cancer.

Keywords: Double-negative T cell; Nrf-2; cell proliferation invasion; pancreatic cancer.