Cryoimmunologic antitumor effects enhanced by dendritic cells in osteosarcoma.

Abstract

We previously reported a limb-salvage technique by treating tumor-bearing bone with liquid nitrogen. We also reported systemic antitumor immunity was enhanced by cryotreatment in a murine osteosarcoma (LM8) model. We therefore combined the cryotreatment of tumor with dendritic cells to promote tumor-specific immune responses. We determined whether our technique could enhance systemic immune response and inhibit metastatic tumor growth in a murine osteosarcoma model. To evaluate activation of the immune response, we prepared six groups of C3H mice (80 mice total): (1) excision only, (2) dendritic cells without reimplantation of the cryotreated primary tumor, (3) reimplantation of the cryotreated primary tumor alone, (4) dendritic cells combined with reimplantation of the cryotreated primary tumor, (5) dendritic cells exposed to cryotreated tumor lysates without reimplantation of the cryotreated primary tumor, and (6) dendritic cells exposed to cryotreated tumor lysates with reimplantation of the cryotreated primary tumor. We then compared and verified the activation state of each group's antitumor immunity. Mice that received dendritic cells exposed to cryotreated tumor lysates with reimplantation of the cryotreated primary tumor group had high serum interferon gamma, reduced pulmonary metastases, and increased numbers of CD8(+) T lymphocytes in the metastatic areas. Combining tumor cryotreatment with dendritic cells enhanced systemic immune responses and inhibited metastatic tumor growth. We suggest immunotherapy could be developed further to improve the treatment of osteosarcoma.