Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma

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

Friction couples in total hip replacement

SummaryThe problem of friction couples remains unresolved to this day. Improvements in femoral and acetabulum implant anchorage over the last 20 years have significantly extended total hip replacement (THR) implant lifespan; the formation of wear debris, however, leads to resorption and osteolysis, considerably shortening implant lifespan in active patients. Alumina–alumina friction couples provide an excellent friction coefficient, with wear particles that do not cause any osteolysis. There is, however, a problem of acetabulum anchorage of solid alumina, and the risk of fracture persists with ceramic implants despite improvements in their mechanical properties. Metal–metal couples also display very good tribological behavior, but at the cost of the formation of Co and Cr ions impacting surrounding bone tissue and accumulating in remote organs. The behavior of such “hard–hard” couples greatly depends on implant component positioning and on the consequences of repeated neck-insert contact. Very highly crosslinked polyethylene (PE) shows very significant improvement in terms of wear at five years’ follow-up compared to conventional PE, but the behavior of this new concept will need to be monitored in the clinical situation if the disappointments experienced with previous hylamer-type improved PE are to be avoided. All these friction couples need to be validated by prospective clinical studies conducted over more than five years, to provide orthopedic surgeons with an eclectic choice of friction couples adapted to the patient's activity