HYPERTHERMIA ENHANCES THE CYTOTOXICITY OF NATIONAL-INSTITUTES-OF-HEALTH 3T3 CELLS TRANSFECTED WITH A NONCLEAVABLE TRANSMEMBRANE PRO-TUMOR NECROSIS FACTOR DELETION MUTANT

Hyperthermia has been shown to potentiate the cytotoxicity of exogenou sly added tumor necrosis factor (TNF) against tumor cell targets. The mechanism for that interaction is not known, but among the possibiliti es are that heat enhances internalization of ligand-bound TNF or enhan ces processing of internalized TNF. In this study, we found that NIH 3 T3 cells transfected with an expression vector containing the full-len gth human pro-TNF secreted TNF and that hyperthermic treatment of chro mium-labeled L929 target cells at 43 degrees C for 1 h potentiated the cytotoxicity of these transfectants against the L929 cells in clonoge nic survival and chromium-release assays. On the other hand, transfect ants expressing a transmembrane, nonsecretable pro-TNF mutant that kil ls L929 cells by cell-to-cell contact without internalization also exh ibited enhanced cytotoxicity against heated L929 cell targets. Thus, p otentiation of the cytotoxicity of TNF by hyperthermia is not strictly dependent on enhanced internalization of ligand-bound TNF or enhanced processing of internalized TNF.