Eliminating roles for T-bet and IL-2 but revealing superior activation and proliferation as mechanisms underpinning dominance of regulatory T cells in tumors.
Oncotarget
; 6(28): 24649-59, 2015 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-26433463
ABSTRACT
Foxp3(+) regulatory T cells (Tregs) are often highly enriched within the tumor-infiltrating T cell pool. Using a well-characterised model of carcinogen-induced fibrosarcomas we show that the enriched tumor-infiltrating Treg population comprises largely of CXCR3(+) T-bet(+) 'TH1-like' Tregs which are thymus-derived Helios(+) cells. Whilst IL-2 maintains homeostatic ratios of Tregs in lymphoid organs, we found that the perturbation in Treg frequencies in tumors is IL-2 independent. Moreover, we show that the TH1 phenotype of tumor-infiltrating Tregs is dispensable for their ability to influence tumor progression. We did however find that unlike Tconvs, the majority of intra-tumoral Tregs express the activation markers CD69, CD25, ICOS, CD103 and CTLA4 and are significantly more proliferative than Tconvs. Moreover, we have found that CD69(+) Tregs are more suppressive than their CD69- counterparts. Collectively, these data indicate superior activation of Tregs in the tumor microenvironment, promoting their suppressive ability and selective proliferation at this site.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcoma Experimental
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Ativação Linfocitária
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Linfócitos do Interstício Tumoral
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Interleucina-2
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Linfócitos T Reguladores
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Proteínas com Domínio T
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Proliferação de Células
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Fibrossarcoma
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article