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Erschienen in: Cancer Immunology, Immunotherapy 7/2007

01.07.2007 | Original Article

Immune reconstitution prevents metastatic recurrence of murine osteosarcoma

verfasst von: Melinda S. Merchant, Fraia Melchionda, Manoj Sinha, Chand Khanna, Lee Helman, Crystal L. Mackall

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2007

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Abstract

Primary tumors developing in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This raises the prospect that metastases derived from such tumors will also evade immunity. To investigate whether immune surveillance plays a role in preventing metastases, we studied a murine model which mimics the clinical progression of osteosarcoma: primary tumor growth in the lower extremity, amputation, minimal residual disease followed by the development of overt metastases. K7M2 implants readily escaped immune surveillance since normal BALB/c mice, T cell deficient SCID and T/NK cell deficient SCID-bg mice showed no difference in the rate of growth of primary osteosarcomas. However, both SCID and SCID-bg mice had higher rates of metastases than immunocompetent mice. Similarly, immune reconstitution following transfer of naive T cells to SCID or SCID-bg mice did not impact primary tumor growth, but significantly diminished metastatic recurrence. T cells in osteosarcoma bearing mice produced IFNγ in response to tumor and IFNγ production by immune reconstituting T cells was required to prevent metastases. These results demonstrate an important role for T cell based immune surveillance in preventing metastases, even when metastases develop from tumors that adeptly evade immunosurveillance. The results further suggest that T cell depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of lymphopenic cancer patients could prevent metastatic recurrence of solid tumors.
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Metadaten
Titel
Immune reconstitution prevents metastatic recurrence of murine osteosarcoma
verfasst von
Melinda S. Merchant
Fraia Melchionda
Manoj Sinha
Chand Khanna
Lee Helman
Crystal L. Mackall
Publikationsdatum
01.07.2007
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 7/2007
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0257-0

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