INDUCTION OF AUTOLOGOUS TUMOR KILLING BY HEAT-TREATMENT OF FRESH HUMAN TUMOR-CELLS - INVOLVEMENT OF GAMMA-DELTA T-CELLS AND HEAT-SHOCK-PROTEIN-70

Autologous tumor killing (ATK) has been implicated as an important pro gnostic factor in cancer patients since the ability of blood lymphocyt es to kill freshly isolated autologous tumor cells was strongly associ ated with good prognosis of the patients, The present study was design ed to induce or enhance ATK sensitivity of fresh human tumor cells by heat stress, Brief exposure of fresh human tumor cells to elevated tem perature increased their susceptibility to lysis by autologous blood l ymphocytes in a short-term Cr-51 release assay, In addition, the heat- elevated ATK sensitivity was confirmed by clonogenic assays, An increa se in ATK was observed with unstimulated lymphocytes in 42% of the cas es and OK432 (streptococcal preparation)-activated lymphocytes in 80% of the cases, Stimulation of blood lymphocytes with autologous, cells and OK432 resulted in an increase in number of gamma delta T cells, wh ich was associated with elevated ATK activity against the stressed tum or cells, At the clonal level, three gamma delta T-cell clones (V gamm a 9/V delta 2+) proliferated in response to autologous, heat-stressed tumor cells and/or OK432 and exhibited elevated cytotoxicity against t he tumor cells, Western blot analysis revealed an increased expression of heat shock protein (HSP) 70 in heat-treated tumor cells, Some of t hem expressed HSP70 on their surfaces, The elevated cytotoxicity again st heat-stressed tumor cells was inhibited by treatment of targets wit h anti-HSP70 monoclonal antibody (mAb) or of effector cells with anti- V delta 2 mAb. Reactivity of gamma delta T cells to autologous, heat-s tressed tumor cells was also inhibited by anti-HSP70 mAb. These result s indicate that exposure to heat of tumor cells induces ATK susceptibi lity, especially to OK432-activated effector cells, and suggest that g amma delta T cells may be involved in ATK against stressed tumor cells through recognition of HSP70 on the target cells.