Paracrine cross-talk between tumor cells and immune cells within the tumor microenvironment underlies local mechanisms of immune evasion. Signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in diverse cancer types, is a key regulator of cytokine and chemokine expression in murine tumors, resulting in suppression of both innate and adaptive antitumor immunity. However, the immunologic effects of STAT3 activation in human cancers have not been studied in detail. To investigate how STAT3 activity in human head and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment to enable immune escape, we used small interfering RNA and small-molecule inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Although conditioned medium containing supernatants from human HNSCC inhibited lipopolysaccharide-induced dendritic cell activation in vitro, supernatants from STAT3-silenced tumor cells reversed this immune evasion mechanism. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention. Cancer Res; 70(16); 6467-76. (C)2010 AACR.
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Cheng, FD
Wang, HW
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Wang, HW
Cuenca, A
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Cuenca, A
Huang, M
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Huang, M
Ghansah, T
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Ghansah, T
Brayer, J
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Brayer, J
Kerr, WG
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Kerr, WG
Takeda, K
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Takeda, K
Akira, S
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Akira, S
Schoenberger, SP
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Schoenberger, SP
Yu, H
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Yu, H
Jove, R
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Jove, R
Sotomayor, EM
论文数: 0引用数: 0
h-index: 0
机构:
Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USAUniv S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
机构:
Univ Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USA
Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA
Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Duffy, Sonia A.
Taylor, Jeremy M. G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Taylor, Jeremy M. G.
Terrell, Jeffrey E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Terrell, Jeffrey E.
Islam, Mozaffarul
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Islam, Mozaffarul
Li, Yun
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Li, Yun
Fowler, Karen E.
论文数: 0引用数: 0
h-index: 0
机构:Univ Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Fowler, Karen E.
Wolf, Gregory T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Wolf, Gregory T.
Teknos, Theodoros N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Cheng, FD
Wang, HW
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Wang, HW
Cuenca, A
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Cuenca, A
Huang, M
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Huang, M
Ghansah, T
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Ghansah, T
Brayer, J
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Brayer, J
Kerr, WG
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Kerr, WG
Takeda, K
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Takeda, K
Akira, S
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Akira, S
Schoenberger, SP
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Schoenberger, SP
Yu, H
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Yu, H
Jove, R
论文数: 0引用数: 0
h-index: 0
机构:Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
Jove, R
Sotomayor, EM
论文数: 0引用数: 0
h-index: 0
机构:
Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USAUniv S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
机构:
Univ Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USA
Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA
Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Duffy, Sonia A.
Taylor, Jeremy M. G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Taylor, Jeremy M. G.
Terrell, Jeffrey E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Terrell, Jeffrey E.
Islam, Mozaffarul
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Islam, Mozaffarul
Li, Yun
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Li, Yun
Fowler, Karen E.
论文数: 0引用数: 0
h-index: 0
机构:Univ Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Fowler, Karen E.
Wolf, Gregory T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA
Wolf, Gregory T.
Teknos, Theodoros N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USAUniv Michigan, Ann Arbor VA HSR&D Ctr Excellence, Dept Otolaryngol, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48113 USA