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J Immunol ; 179(4): 2627-33, 2007 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-17675526

RESUMEN

The overall prevalence with which endogenous tumor Ags induce host T cell responses is unclear. Even when such responses are detected, they do not usually result in spontaneous remission of the cancer. We hypothesized that this might be associated with a predominant phenotype and/or cytokine profile of tumor-specific responses that is different from protective T cell responses to other chronic Ags, such as CMV. We detected significant T cell responses to CEA, HER-2/neu, and/or MAGE-A3 in 17 of 21 breast cancer patients naive to immunotherapy. The pattern of T cell cytokines produced in response to tumor-associated Ags (TAAs) in breast cancer patients was significantly different from that produced in response to CMV or influenza in the same patients. Specifically, there was a higher proportion of IL-2-producing CD8(+) T cells, and a lower proportion of IFN-gamma-producing CD4(+) and/or CD8(+) T cells responding to TAAs compared with CMV or influenza Ags. Finally, the phenotype of TAA-responsive CD8(+) T cells in breast cancer patients was almost completely CD28(+)CD45RA(-) (memory phenotype). CMV-responsive CD8(+) T cells in the same patients were broadly distributed among phenotypes, and contained a high proportion of terminal effector cells (CD27(-)CD28(-)CD45RA(+)) that were absent in the TAA responses. Taken together, these results suggest that TAA-responsive T cells are induced in breast cancer patients, but those T cells are phenotypically and functionally different from CMV- or influenza-responsive T cells. Immunotherapies directed against TAAs may need to alter these T cell signatures to be effective.


Asunto(s)
Antígenos CD/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/inmunología , Linfocitos T CD8-positivos/inmunología , Citocinas/inmunología , Adulto , Antígenos Virales/inmunología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Linfocitos T CD8-positivos/patología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Femenino , Humanos , Inmunoterapia , Gripe Humana/inmunología , Gripe Humana/patología , Masculino , Persona de Mediana Edad
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