Cryoimmunologic antitumor effects enhanced by dendritic cells in osteosarcoma.
BACKGROUND
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.


OBJECTIVE
We determined whether our technique could enhance systemic immune response and inhibit metastatic tumor growth in a murine osteosarcoma model.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Combining tumor cryotreatment with dendritic cells enhanced systemic immune responses and inhibited metastatic tumor growth.


CONCLUSIONS
We suggest immunotherapy could be developed further to improve the treatment of osteosarcoma.
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Masanori
M
Kawano
Hideji
H
Nishida
Yasunari
Y
Nakamoto
Hiroshi
H
Tsumura
Hiroyuki
H
Tsuchiya
D000818:Animals; D045744:Cell Line, Tumor; D017690:Cell Transplantation / Q000379:methods*; D017679:Cryotherapy / Q000379:methods*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D007111:Immunity, Cellular; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental; D012516:Osteosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012092:Replantation / Q000379:methods*; D016896:Treatment Outcome