Heat-shock protein 72 in human osteosarcoma: T-lymphocyte reactivity and cytotoxicity

Heat-shock proteins (hsp) have been shown to be involved in tumor immunity. The expression of hsp72, the inducible form of the 70-kDa family, is incre ased in human osteosarcoma and correlates with a good response to neoadjuva nt chemotherapy. It is selectively expressed on the surface of osteosarcoma cell lines where it acts as a target molecule for natural killer cells. Be cause hsps are strongly immunogenic, this study investigates the role of hs ps as antigens in human osteosarcoma. Osteosarcoma cells and infiltrating T lymphocytes were isolated from osteosarcoma specimens from 3 patients with high-grade osteosarcoma. Two of the tumors immunohistochemically expressed hsp72, whereas one did not. T-cell lines isolated from both hsp72-positive osteosarcomas had a significantly proliferative response upon stimulation with recombinant human hsp72, whereas the T lymphocytes from the hsp72-nega tive osteosarcoma did not recognize hsp72. The lines had a significantly pr oliferative response upon stimulation with autologous osteosarcoma cells an d exerted cytotoxicity. Cytotoxicity and proliferation could be increased b y heat treatment of the target cell in the hsp72 responsive lines. These re sults demonstrate that hsp72 is involved in the interaction of T lymphocyte s and osteosarcoma cells in a specific group of osteosarcomas expressing hs p72. Because of the cytotoxic potential of these T lymphocytes, induction o f hsp72 in osteosarcomas might lead to an increased immune response and rej ection of the osteosarcoma.