Fas Ligand Deficiency Impairs Tumor Immunity by Promoting an Accumulation of Monocytic Myeloid-Derived Suppressor Cells

被引：34

作者：

Peyvandi, Sanam ^{[1
,2
]}

Buart, Stephanie ^{[1
,2
]}

Samah, Boubekeur ^{[1
,2
]}

Vetizou, Marie ^{[1
,2
]}

Zhang, Yanyan ^{[2
,3
]}

Durrieu, Ludovic ^{[1
,2
]}

Polrot, Melanie ^{[4
]}

Chouaib, Salem ^{[1
,2
]}

Benihoud, Karim ^{[5
,6
]}

Louache, Fawzia ^{[2
]}

Karray, Saoussen ^{[1
,2
]}

机构：

[1] INSERM, U753, Gustave Roussy Campus, Villejuif, France

[2] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France

[3] INSERM, U1170, Gustave Roussy Campus, Villejuif, France

[4] Gustave Roussy Campus, Preclin Evaluat Platform PFEP, Villejuif, France

[5] CNRS, Gustave Roussy Campus, UMR 8203, Villejuif, France

[6] Univ Paris 11, Orsay, France

来源：

CANCER RESEARCH | 2015年 / 75卷 / 20期

关键词：

DEATH; CANCER; LYMPHOPROLIFERATION; MICROENVIRONMENT; DIFFERENTIATION; INHIBITION; CARCINOMA; ANTIGEN; INDUCE; SAFETY;

D O I：

10.1158/0008-5472.CAN-14-1848

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naive mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid-derived suppressor cells (MDSC) in mice bearing Lewis lung carcinoma tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL-deficient displayed an enhanced proportion of tumor-associated macrophages and regulatory T cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role for FasL in modulating immuno-suppressive cells. (C) 2015 AACR.

引用

页码：4292 / 4301

页数：10

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