Adaptive Modulation of MHC Class I Expression and Immune Evasion to Cytotoxic Immunocytes in Cancer Cells

Abstract

It has been well-demonstrated that cancer cells can escape from the immune surveillance of Cytotoxic T lymphocytes (CTL) and natural killer cells (NK cells) by modulating their MHC class I expression. In order to get insight into the mechanism in which cancer cells regulate their MHC class I expression in response to the attack of CTL and NK cells, different concentration of effector cells were used to examine the effects of low effector/target ratio on the MHC class I expression shifting, tanswells were used to separate effector cells and target cells in culture to check if the cell to cell contact is required for the MHC class I expression shifting, and intracellular flow cytometry was used to determine if MHC class I protein synthesis in cancer cells were also changed with their surface antigen in current studies. Our data indicate that (1) both elimination of target cells and direct regulation of MHC class I expression in target cells contributed to modulation of MHC class I expression in cancer cells (2) effector cell mediated-regulation of MHC class I expression in cancer cells required cell to cell contact (3) the shifting of surface MHC class I antigen on the cancer cells might be caused by the change of MHC class I protein synthesis in cancer cells and (4) application of inadequate numbers of effector cells may induce immune evasion of cancer cells, a cautionary tale for future clinical studies