American Association for Cancer Research
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Supplementary Figure 1 from Inhibitory Roles of Signal Transducer and Activator of Transcription 3 in Antitumor Immunity during Carcinogen-Induced Lung Tumorigenesis

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journal contribution
posted on 2023-03-30, 21:12 authored by Shoichi Ihara, Hiroshi Kida, Hisashi Arase, Lokesh P. Tripathi, Yi-An Chen, Tetsuya Kimura, Mitsuhiro Yoshida, Yozo Kashiwa, Haruhiko Hirata, Reiko Fukamizu, Ruriko Inoue, Kana Hasegawa, Sho Goya, Ryo Takahashi, Toshiyuki Minami, Kazuyuki Tsujino, Mayumi Suzuki, Satoshi Kohmo, Koji Inoue, Izumi Nagatomo, Yoshito Takeda, Takashi Kijima, Kenji Mizuguchi, Isao Tachibana, Atsushi Kumanogoh

PDF file - 41K, Stat3delta/delta did not acquire large tumors compared to Stat3flox/flox mice



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 (Stat3Δ/Δ) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3Δ/Δ 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 Stat3Δ/Δ 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. ©2012 AACR.

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