Follicular B Lymphomas Generate Regulatory T Cells via the ICOS/ICOSL Pathway and Are Susceptible to Treatment by Anti-ICOS/ICOSL Therapy.
Cancer Res
; 76(16): 4648-60, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27246829
ABSTRACT
The prognosis of follicular lymphoma (FL) patients is suspected to be influenced by tumor-infiltrating regulatory T cells (Treg). The mechanism of Treg enrichment in FL and their impact on malignant FL B cells remains to be elucidated. We analyzed 46 fresh lymph node biopsy samples, including FL (n = 20), diffuse large B-cell lymphoma (n = 10), classical Hodgkin lymphoma (n = 9), and reactive lymphadenitis (n = 7). Using multicolor flow cytometry and cell sorting, we observed an accumulation of CD25(high)CD127(low/neg) Tregs in FL tissues. These Tregs comprised activated ICOS(+) Tregs that were able to suppress not only conventional T cells, but also FL B cells. These FL B cells were able to express ICOSL in vitro and to generate CD25(high)FoxP3(high) Tregs expressing ICOS. Treg generation was associated with ICOS/ICOSL engagement and was abrogated by antagonist anti-ICOS and anti-ICOSL antibodies. Interactions between Tregs and FL B cells resulted in ICOSL downregulation on FL B cells. Our results highlight a key role for Tregs in FL pathogenesis and suggest that targeting the ICOS/ICOSL pathway may be a promising immunotherapy for FL treatment. Cancer Res; 76(16); 4648-60. ©2016 AACR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
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Linfoma de Células B
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Linfócitos T Reguladores
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Ligante Coestimulador de Linfócitos T Induzíveis
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Proteína Coestimuladora de Linfócitos T Induzíveis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França