Transforming Growth Factor-[beta] and Tumor Necrosis Factor-[alpha] Reduce the Sensitivity of MiaPaCa2 Pancreatic Cancer Cells to Lysis by NK Cells

We studied the role of cytokines TGF-[beta] and TNF[alpha] in reduction of the cytolytic activity of NK cells towards tumor cells. Exogenous TGF-[beta] and TNF[alpha] reduced the sensitivity of MiaPaCa2 pancreatic adenocarcinoma cells to NK cytotoxicity, which was associated with reduction of ULBP-1 expression and increase of HLA-E, HLA-G, CD155, and CD112 expression on MiaPaCa2 cells. Changes in the expression of ligands for NK receptors on tumor cells induced by TGF-[beta] and TNF[alpha] may contribute to reduction of cytotoxicity of tumor-associated NK cells and thus prevent an adequate antitumor immune response leading to the disease progress. Key Words: pancreatic adenocarcinoma cells; natural killer cells; cytotoxicity; transforming growth factor-[beta]; tumor necrosis factor-[alpha]