The role of STAT3 activation in modulating the immune microenvironment of GBM

被引：51

作者：

See, Alfred P.

Han, James E. ^{[1
]}

Phallen, Jillian ^{[1
]}

Binder, Zev ^{[2
,3
,4
]}

Gallia, Gary ^{[2
]}

Pan, Fan ^{[5
]}

Jinasena, Dilini ^{[5
]}

Jackson, Christopher

Belcaid, Zineb ^{[1
]}

Jeong, Sung Jin ^{[1
]}

Gottschalk, Chelsea ^{[1
]}

Zeng, Jing ^{[6
]}

Ruzevick, Jacob

Nicholas, Sarah ^{[1
]}

Kim, Young ^{[7
]}

Albesiano, Emilia ^{[5
]}

Pardoll, Drew M. ^{[5
]}

Lim, Michael ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Johns Hopkins Hosp, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Ludwig Collaborat Lab, Dept Neurosurg, Baltimore, MD 21231 USA

[3] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA

[4] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA

[5] Johns Hopkins Univ, Sch Med, Immunol & Hematopoiesis Div,Dept Oncol & Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[6] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[7] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21231 USA

来源：

JOURNAL OF NEURO-ONCOLOGY | 2012年 / 110卷 / 03期

关键词：

Glioblastoma multiforme (GBM); Signal transducer and activator of transcription 3 (STAT3); Small molecule inhibitor; Immunotherapy; REGULATORY T-CELLS; SMALL-MOLECULE INHIBITOR; EPIDERMAL-GROWTH-FACTOR; DENDRITIC CELLS; GLIOBLASTOMA-MULTIFORME; CONSTITUTIVE ACTIVATION; TUMOR MICROENVIRONMENT; SIGNAL TRANSDUCERS; MALIGNANT GLIOMA; GENE-EXPRESSION;

D O I：

10.1007/s11060-012-0981-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma multiforme (GBM) modulates the immune system to engance its malignant potential. Signal transducer and activator of transcription 3 (STAT3) activation is a regulatory node in modulating the immune microenvironment in several human tumors, including GBM. To investigate whether STAT3 inhibition might enhance anti-tumor responses, we inhibited STAT3 signaling using small interfering RNA against STAT3. We tested the human GBM cell lines U87, U251, and HS683, which are known to constitutively express high levels of phospho-STAT3. STAT3 inhibition resulted in enhanced expression of several pro-inflammatory cytokines and chemokines and supernatants from STAT3-silenced human GBM cell lines increased lipopolysaccharide-induced dendritic cell activation in vitro. We obtained comparable results when STAT3 activity was suppressed with specific small molecule inhibitors. Our results support the hypothesis that activated STAT3 contributes to the immunosuppressive microenvironment in GBM and support previous studies implicating STAT3 as a potential target for immunotherapy.

引用

页码：359 / 368

页数：10