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Cancer Res. 2016 Aug 15;76(16):4648-60. doi: 10.1158/0008-5472.CAN-15-0589. Epub 2016 May 31.

Follicular B Lymphomas Generate Regulatory T Cells via the ICOS/ICOSL Pathway and Are Susceptible to Treatment by Anti-ICOS/ICOSL Therapy.

Author information

1
Centre de recherche en Cancérologie de Marseille, Inserm U1068/CNRS U7258, Marseille, France. Aix Marseille Université, Marseille, France.
2
Centre de recherche en Cancérologie de Marseille, Inserm U1068/CNRS U7258, Marseille, France. Institut Paoli - Calmettes, Marseille, France.
3
Institut Paoli - Calmettes, Marseille, France.
4
Centre de recherche en Cancérologie de Marseille, Inserm U1068/CNRS U7258, Marseille, France.
5
Centre de Recherche en Cancérologie de Lyon, Inserm U1052/CNRS 5286, Lyon, France.
6
Institut Albert Bonniot, Grenoble, France.
7
Centre de recherche en Cancérologie de Marseille, Inserm U1068/CNRS U7258, Marseille, France. Aix Marseille Université, Marseille, France. Institut Paoli - Calmettes, Marseille, France.
8
Centre de recherche en Cancérologie de Marseille, Inserm U1068/CNRS U7258, Marseille, France. Aix Marseille Université, Marseille, France. Institut Paoli - Calmettes, Marseille, France. daniel.olive@inserm.fr.

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.

PMID:
27246829
DOI:
10.1158/0008-5472.CAN-15-0589
[Indexed for MEDLINE]
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