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Open Access 01-04-2011 | Original Article

Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells

Authors: Emilie P. Buddingh, Marco W. Schilham, S. Eriaty N. Ruslan, Dagmar Berghuis, Karoly Szuhai, Jolien Suurmond, Antonie H. M. Taminiau, Hans Gelderblom, R. Maarten Egeler, Massimo Serra, Pancras C. W. Hogendoorn, Arjan C. Lankester

Published in: Cancer Immunology, Immunotherapy | Issue 4/2011

Abstract

High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma.

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Title: Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells
Authors: Emilie P. Buddingh
Marco W. Schilham
S. Eriaty N. Ruslan
Dagmar Berghuis
Karoly Szuhai
Jolien Suurmond
Antonie H. M. Taminiau
Hans Gelderblom
R. Maarten Egeler
Massimo Serra
Pancras C. W. Hogendoorn
Arjan C. Lankester
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 4/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0965-3

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