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Background: Osteosarcoma is the most common type of primary bone tumor. The use of\ud aggressive chemotherapy has drastically improved the prognosis of the patients with nonmetastatic\ud osteosarcomas, however the prognosis of the patients with metastasis is still very poor.\ud Then, new and more effective treatments for curing osteosarcoma, such as immunotherapy are\ud needed. Tumor-infiltrating lymphocytes (TIL) have been involved in the control of tumor\ud development and already assessed with success for the treatment of several cancers including\ud melanoma. While TIL represent a fascinating therapeutic approach in numerous malignant\ud pathologies, there is few report concerning adult bone-associated tumors including osteosarcoma.\ud Methods: Human TIL were isolated and characterized (phenotype, lytic activity) from twentyseven\ud patients with bone-associated tumors (osteosarcoma, Ewing's sarcoma, giant cell tumor,\ud chondrosarcoma, plasmocytoma and bone metastases). Similar experiments were performed using\ud rat osteosarcoma model.\ud Results: While TIL with a main CD4+ profile were easily isolated from most of the tumor samples,\ud only TIL extracted from osteosarcoma were cytotoxic against allogeneic tumor cells. In all cases,\ud TIL lytic activity was significantly higher compared to autologous peripheral blood leukocytes.\ud Similar data were observed in rat osteosarcoma model where TIL were characterized by a main\ud CD4+ profile and high lytic activity against allogeneic and autologous tumor cells. Moreover, rat TIL\ud expansion was not accompanied by refractoriness to further activation stimulus mainly by tumor\ud antigens.\ud Conclusion: These results demonstrated that TIL therapy could be a very efficient strategy for\ud the treatment of adult osteosarcoma. |
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