Regulation of arachidonic acid in esophageal adenocarcinoma cells and tumor-infiltrating lymphocytes.

The generation and development of esophageal adenocarcinoma (EAC) are correlated with neuroimmunological factors. The aim of this study was to observe the effectiveness of the neurotransmitter arachidonic acid (AA) on two EAC cell lines, OE19 and SK-GT-4, as well as three isolated tumor-infiltrating lymphocytes (TIL1, 2 and 3). C-X-C chemokine receptor type 4 (CXCR-4) and tumor necrosis factor receptor 1 (TNFR1) expression, cell migration, necrosis, cytokine secretion and cytotoxicity of TILs were investigated. AA dose-dependently increased the migration of all cells. However, AA did not increase the percentage of cell death of the three TILs in the presence of a necrosis-inducing agent. AA dose-dependently increased the cytotoxicity of the three γδT cell-enriched TILs compared with the OE19 and SK-GT-4 cell lines. AA also dose-dependently increased the secretion of interferon-γ (IFN-γ) and TNF-β in TIL1 and 2. However, the cytokine secretion and cytotoxicity activity of TIL3 and γδT cell-enriched TIL3 were the lowest. Furthermore, the percentage of CD4+forkhead box p3 (Foxp3)+ regulatory T cells in TIL3 was the highest. The effect of AA on tumor cells and TILs is different. The degree of malignancy of the tumor and the ratio of regulatory T cells may be the main factors determining the function of AA.