Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
PLoS One
; 7(1): e30793, 2012.
Article
en En
| MEDLINE
| ID: mdl-22292042
ABSTRACT
FoxP3(+) T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3(+) regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3(+) T cells. We found that only memory, but not naïve, FoxP3(+) T cells are highly enriched in tumors. Almost all of the tumor-infiltrating FoxP3(+) T cells express Helios, an antigen associated either with thymus-generated FoxP3(+) T cells or activated T cells in the periphery. The tumor-infiltrating FoxP3(+) T cells largely lack CD62L and CCR7, two trafficking receptors required for T cell migration into secondary lymphoid tissues. Instead, the tumor infiltrating FoxP3(+) T cells highly express memory/tumor-associated CCR8 and CXCR4. Antigen priming is required for induction of this trafficking receptor phenotype in FoxP3(+) T cells and only antigen primed, but not antigen-inexperienced naive, FoxP3(+) T cells can efficiently migrate into tumors. While the migration of FoxP3(+) T cells into tumors was a readily detectable event, generation of induced FoxP3(+) T cells within tumors was unexpectedly inefficient. Genetic marking of current and ex-FoxP3(+) T cells revealed that tumor-infiltrating FoxP3(+) T cells are highly stable and do not readily convert back to FoxP3(-) T cells. Taken together, our results indicate that population of tumors with thymus-generated FoxP3(+) T cells requires an antigen priming-dependent trafficking receptor switch in lymphoid tissues.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Reguladores
/
Receptores de Quimiocina
/
Factores de Transcripción Forkhead
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Neoplasias
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article