TUMOR-NECROSIS-FACTOR-ALPHA INDUCES AN INCREASE IN SUSCEPTIBILITY OF HUMAN GLIOBLASTOMA U87-MG CELLS TO NATURAL-KILLER CELL-MEDIATED LYSIS

The mechanism by which tumour necrosis factor (TNF)-alpha increases th e susceptibility of U87-MG human glioblastoma cells to lysis by natura l killer (NK) cells was studied. Treatment with TNF-alpha (100 units m l-1) for 48 h enhanced the susceptibility of tumour cells to lysis by NK cells. Increased susceptibility to lysis was associated with enhanc ed expression of intercellular adhesion molecule 1 (ICAM-1) and HLA cl ass I antigen. Antisense ICAM-1 oligonucleotide inhibited lysis by NK cells of TNF-alpha-treated tumour cells. In contrast, acid treatment f ollowing TNF-alpha treatment increased lysis by NK cells. These findin gs indicate that TNF-alpha treatment of glioblastoma cells increased t heir susceptibility to lysis by NK cells, since ICAM-1 up-regulation w ould have more profound effects on NK susceptibility than would HLA cl ass I antigen up-regulation.