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

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.

Le KS ，Thibult ML ，Just-Landi S ，Pastor S ，Gondois-Rey F ，Granjeaud S ，Broussais F ，Bouabdallah R ，Colisson R ，Caux C ，Ménétrier-Caux C ，Leroux D ，Xerri L ，Olive D ... -  《-》

Acute Myeloid Leukemia Cells Express ICOS Ligand to Promote the Expansion of Regulatory T Cells.

Han Y ，Dong Y ，Yang Q ，Xu W ，Jiang S ，Yu Z ，Yu K ，Zhang S ... -  《Frontiers in Immunology》

MiR21 sensitized B-lymphoma cells to ABT-199 via ICOS/ICOSL-mediated interaction of Treg cells with endothelial cells.

Zheng Z ，Xu PP ，Wang L ，Zhao HJ ，Weng XQ ，Zhong HJ ，Qu B ，Xiong J ，Zhao Y ，Wang XF ，Janin A ，Zhao WL ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Augmented ICOS expression in patients with early diffuse cutaneous systemic sclerosis.

Hasegawa M ，Fujimoto M ，Matsushita T ，Hamaguchi Y ，Takehara K ... -  《-》

Protective Role of ICOS and ICOS Ligand in Corneal Transplantation and in Maintenance of Immune Privilege.

Kunishige T ，Taniguchi H ，Terada M ，Akiba H ，Yagita H ，Abe R ，Hori J ... -  《-》