Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein

被引：717

作者：

Cheng, Pingyan ^{[1
]}

Corzo, Cesar A. ^{[1
]}

Luetteke, Noreen ^{[1
]}

Yu, Bin ^{[1
]}

Nagaraj, Srinivas ^{[1
]}

Bui, Marylin M. ^{[1
]}

Ortiz, Myrna ^{[1
]}

Nacken, Wolfgang ^{[3
]}

Sorg, Clemens ^{[2
]}

Vogl, Thomas ^{[2
]}

Roth, Johannes ^{[2
]}

Gabrilovich, Dmitry I. ^{[1
]}

机构：

[1] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA

[2] Univ Munster, Inst Immunol, D-48149 Munster, Germany

[3] Ctr Mol Biol Inflammat, Inst Mol Virol, D-48149 Munster, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2008年 / 205卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1084/jem.20080132

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.

引用

页码：2235 / 2249

页数：15

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