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

被引：0

作者：

Alfred P. See

James E. Han

Jillian Phallen

Zev Binder

Gary Gallia

Fan Pan

Dilini Jinasena

Christopher Jackson

Zineb Belcaid

Sung Jin Jeong

Chelsea Gottschalk

Jing Zeng

Jacob Ruzevick

Sarah Nicholas

Young Kim

Emilia Albesiano

Drew M. Pardoll

Michael Lim

机构：

[1] Johns Hopkins University School of Medicine,Department of Neurosurgery

[2] The Johns Hopkins Hospital,Ludwig Collaborative Laboratory, Department of Neurosurgery

[3] Johns Hopkins University School of Medicine,Johns Hopkins Physical Sciences in Oncology Center and Institute for NanoBioTechnology

[4] Johns Hopkins University School of Medicine,Immunology and Hematopoiesis Division, Department of Oncology and Medicine, Sidney Kimmel Comprehensive Cancer Center

[5] Johns Hopkins University,Department of Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center

[6] Johns Hopkins University School of Medicine,Department of Otolaryngology

[7] Johns Hopkins University,Head and Neck Surgery, Oncology

[8] Johns Hopkins University School of Medicine,undefined

来源：

Journal of Neuro-Oncology | 2012年 / 110卷

关键词：

Glioblastoma multiforme (GBM); Signal transducer and activator of transcription 3 (STAT3); Small molecule inhibitor; Immunotherapy;

D O I：

暂无

中图分类号：

学科分类号：

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：9

共 310 条

[1]

Prasad G(2004)Recent advances in experimental molecular therapeutics for malignant gliomas Curr Med Chem Anticancer Agents 4 347-361

[2]

Wang H(2005)Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain Lab Invest 85 328-341

[3]

Hill DL(2007)Loss of tumor suppressor PTEN function increases B7–H1 expression and immunoresistance in glioma Nat Med 13 84-88

[4]

Zhang R(2004)Induction of a CD4(+) T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma J Immunol 173 4352-4359

[5]

Zagzag D(2002)Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells Oncogene 21 8404-8413

[6]

Salnikow K(2005)Targeting STAT3 affects melanoma on multiple fronts Cancer Metastasis Rev 24 315-327

[7]

Chiriboga L(2004)Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma World J Gastroenterol 10 1569-1573

[8]

Yee H(2009)STATs in cancer inflammation and immunity: a leading role for STAT3 Nat Rev Cancer 9 798-809

[9]

Lan L(2004)Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells Nat Med 10 48-54

[10]

Ali MA(2007)Distinct roles of different NF-kappa B subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells J Immunol 178 6777-6788

← 1 2 3 4 5 6 7 8 9 10 →