INTERFERON-GAMMA INDUCES A DECREASE IN THE SUSCEPTIBILITY OF HUMAN GLIOMA-CELLS TO LYSIS BY LYMPHOKINE-ACTIVATED KILLER-CELLS

WE STUDIED THE effect that treating two types of glioblastoma cell lin es, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their sus ceptibility to lysis by lymphokine-activated killer (LAK) cells. We al so examined the participation of cell-adhesion molecules and major his tocompatibility complex (MHC) class I and II antigens present on the t arget cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml ) for 48 hours resulted in the increased expression of both intercellu lar-adhesion molecule 1 and MHC class I antigens on tumor cells. In ad dition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affect ed by IFN-gamma treatment. These changes in expression were accompanie d by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further in hibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-g amma increased their susceptibility to lysis by LAK cells. These findi ngs suggest that treatment of glioblastoma cells with IFN-gamma decrea sed their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expres sion of MHC class I antigen on target cells.