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 prognostic factor in cancer patients since the ability of blood lymphocytes to kill freshly isolated autologous tumor cells was strongly associated with good prognosis of the patients. The present study was designed to induce or enhance ATK sensitivity of fresh human tumor cells by heat stress. Brief exposure of fresh human tumor cells to elevated temperature increased their susceptibility to lysis by autologous blood lymphocytes in a short-term (51)Cr release assay. In addition, the heat-elevated ATK sensitivity was confirmed by clonogenic assays. An increase in ATK was observed with unstimulated lymphocytes in 42% of the cases and OK432 (streptococcal preparation)-activated lymphocytes in 80% of the cases. Stimulation of blood lymphocytes with autologous, heat-stressed tumor cells and OK432 resulted in an increase in number of gamma delta T cells, which was associated with elevated ATK activity against the stressed tumor cells. At the clonal level, three gamma delta T-cell clones (V gamma 9/V delta 2+) proliferated in response to autologous, heat stressed tumor cells and/or OK432 and exhibited elevated cytotoxicity against the tumor cells. Western blot analysis revealed an increased expression of heat shock protein (HSP) 70 in heat- treated tumor cells. Some of them expressed HSP70 on their surfaces. The elevated cytoxicity against heat-stressed tumor cells was inhibited by treatment of targets with anti-HSP70 monoclonal antibody (mAb) or of effector cells with anti-V delta2 mAb. Reactivity of gamma delta T cells to autologous, heat- stressed tumor cells was also inhibited by anti-HSP70 mAb. These results indicate that exposure to heat of tumor cells induces ATK susceptibility, especially to OK432-activated effector cells, and suggest that gamma delta T cells may be involved in ATK against stressed tumor cells through recognition of HSP70 on the target cells.
Wei
Y
Y
Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Japan.
Zhao
X
X
Kariya
Y
Y
Fukata
H
H
Teshigawara
K
K
Uchida
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010844:Picibanil / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D010844:Picibanil