Transforming Growth Factor-β and Tumor Necrosis Factor-α Reduce the Sensitivity of MiaPaCa2 Pancreatic Cancer Cells to Lysis by NK Cells

Abstract

We studied the role of cytokines TGF-β and TNFα in reduction of the cytolytic activity of NK cells towards tumor cells. Exogenous TGF-β and TNFα 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 Mia-PaCa2 cells. Changes in the expression of ligands for NK receptors on tumor cells induced by TGF-β and TNFα may contribute to reduction of cytotoxicity of tumor-associated NK cells and thus prevent an adequate antitumor immune response leading to the disease progress.