Mammary tumors with diverse immunological phenotypes show differing sensitivity to adoptively transferred CD8+ T cells lacking the Cbl-b gene.
Cancer Immunol Immunother
; 58(11): 1865-75, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19350239
ABSTRACT
We tested the efficacy of CD8+ T cells lacking the Cbl-b gene against a panel of mammary tumor lines with different intrinsic sensitivities to T cells. Mice bearing established tumors expressing an ovalbumin-tagged version of HER-2/neu underwent adoptive transfer with Cbl-b-replete or -null CD8+ T cells from OT-I T cell receptor transgenic donor mice. In general, Cbl-b-null OT-I cells showed enhanced expansion, persistence, and capacity for tumor infiltration. This resulted in markedly enhanced efficacy against two tumor lines that normally demonstrate complete (NOP21) or partial (NOP23) regression. Moreover, a third tumor line (NOP6) that normally demonstrates progressive disease underwent complete regression in response to Cbl-b-null OT-I cells. However, a fourth tumor line (NOP18) was resistant to Cbl-b-null OT-I cells owing to a profound barrier to lymphocyte infiltration. Thus, Cbl-b-null CD8+ T cells are generally more efficacious but are nonetheless unable to mediate curative responses against all tumor phenotypes.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
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Transferência Adotiva
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Proto-Oncogênicas c-cbl
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Neoplasias Mamárias Experimentais
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article