Inhibitory Roles of Signal Transducer and Activator of Transcription 3 in Antitumor Immunity during Carcinogen-Induced Lung Tumorigenesis

被引：74

作者：

Ihara, Shoichi ^{[1
]}

Kida, Hiroshi ^{[1
]}

Arase, Hisashi ^{[2
]}

Tripathi, Lokesh P. ^{[6
,7
]}

Chen, Yi-An ^{[5
,6
,7
]}

Kimura, Tetsuya ^{[1
,3
,4
]}

Yoshida, Mitsuhiro ^{[1
]}

Kashiwa, Yozo ^{[1
]}

Hirata, Haruhiko ^{[1
]}

Fukamizu, Reiko ^{[1
]}

Inoue, Ruriko ^{[1
]}

Hasegawa, Kana ^{[1
]}

Goya, Sho ^{[1
]}

Takahashi, Ryo ^{[1
]}

Minami, Toshiyuki ^{[1
]}

Tsujino, Kazuyuki ^{[1
]}

Suzuki, Mayumi ^{[1
]}

Kohmo, Satoshi ^{[1
]}

Inoue, Koji ^{[1
]}

Nagatomo, Izumi ^{[1
]}

Takeda, Yoshito ^{[1
]}

Kijima, Takashi ^{[1
]}

Mizuguchi, Kenji ^{[5
,6
,7
]}

Tachibana, Isao ^{[1
]}

Kumanogoh, Atsushi ^{[1
,3
,4
]}

机构：

[1] Osaka Univ, Dept Resp Med Allergy & Rheumat Dis, Grad Sch Med, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Lab Immunochem, World Premier Int Res Ctr WPI, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Dept Immunopathol, World Premier Int Res Ctr WPI, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[4] Osaka Univ, Dept Immunochem, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan

[6] Natl Inst Biomed Innovat, Osaka, Japan

[7] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Honcho Kawaguchi, Saitama, Japan

来源：

CANCER RESEARCH | 2012年 / 72卷 / 12期

关键词：

EPITHELIAL-CELLS; STAT3; ACTIVATION; IN-VIVO; INFLAMMATION; CANCER; EXPRESSION; APOPTOSIS; SURVIVAL; PATHWAY; IL-6;

D O I：

10.1158/0008-5472.CAN-11-4062

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Stat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3(Delta/Delta)) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3(Delta/Delta) mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3(Delta/Delta) tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non-small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell-mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis. Cancer Res; 72(12); 2990-9. (C)2012 AACR.

引用

页码：2990 / 2999

页数：10

共 45 条

[1]

DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction [J].