title: Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma.
abstract: 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.
  
  
  CONCLUSIONS
  These results demonstrated that TIL therapy could be a very efficient strategy for the treatment of adult osteosarcoma.
authors.affiliation: INSERM ERI 7-EA 3822, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 Rue Gaston Veil, 44035 Nantes Cedex 1, France. sandrine.theoleyre@univ-nantes.fr
authors.forename: S
authors.initials: S
authors.lastname: Théoleyre
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: B
authors.initials: B
authors.lastname: Cherrier
authors.forename: N
authors.initials: N
authors.lastname: Passuti
authors.forename: F
authors.initials: F
authors.lastname: Gouin
authors.forename: F
authors.initials: F
authors.lastname: Rédini
authors.forename: D
authors.initials: D
authors.lastname: Heymann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007962:Leukocytes / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology; D008297:Male; D008545:Melanoma / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010014:Osteolysis; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D051381:Rats