Activated CD69+ T cells foster immune privilege by regulating IDO expression in tumor-associated macrophages.
J Immunol
; 188(3): 1117-24, 2012 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-22184722
ABSTRACT
Substantial evidence indicates that immune activation at stroma can be rerouted in a tumor-promoting direction. CD69 is an immunoregulatory molecule expressed by early-activated leukocytes at sites of chronic inflammation, and CD69(+) T cells have been found to promote human tumor progression. In this study, we showed that, upon encountering autologous CD69(+) T cells, tumor macrophages (MΦs) acquired the ability to produce much greater amounts of IDO protein in cancer nests. The T cells isolated from the hepatocellular carcinoma tissues expressed significantly more CD69 molecules than did those on paired circulating and nontumor-infiltrating T cells; these tumor-derived CD69(+) T cells could induce considerable IDO in monocytes. Interestingly, the tumor-associated monocytes/MΦs isolated from hepatocellular carcinoma tissues or generated by in vitro culture effectively activated circulating T cells to express CD69. IL-12 derived from tumor MΦs was required for early T cell activation and subsequent IDO expression. Moreover, we found that conditioned medium from IDO(+) MΦs effectively suppressed T cell responses in vitro, an effect that could be reversed by adding extrinsic IDO substrate tryptophan or by pretreating MΦs with an IDO inhibitor 1-methyl-DL-tryptophan. These data revealed a fine-tuned collaborative action between different types of immune cells to counteract T cell responses in tumor microenvironment. Such an active induction of immune tolerance should be considered for the rational design of effective immune-based anticancer therapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Antígenos de Diferenciación de Linfocitos T
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Antígenos CD
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Carcinoma Hepatocelular
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Lectinas Tipo C
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Indolamina-Pirrol 2,3,-Dioxigenasa
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Tolerancia Inmunológica
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Macrófagos
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2012
Tipo del documento:
Article