Yq. Wei et al., INDUCTION OF AUTOLOGOUS TUMOR KILLING BY HEAT-TREATMENT OF FRESH HUMAN TUMOR-CELLS - INVOLVEMENT OF GAMMA-DELTA T-CELLS AND HEAT-SHOCK-PROTEIN-70, Cancer research, 56(5), 1996, pp. 1104-1110
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.