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Hokkaido University Collection of Scholarly and Academic Papers >
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Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling
| Title: | Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling |
| Authors: | Moriguchi, Tetsuo Browse this author →KAKEN DB | | Kaneumi, Shun Browse this author | | Takeda, Shuji Browse this author | | Enomoto, Kei Browse this author | | Mishra, Shyam Kumar Browse this author | | Miki, Tetsuro Browse this author | | Koshimizu, Uichi Browse this author | | Kitamura, Hidemitsu Browse this author →KAKEN DB | | Kondo, Toru Browse this author →KAKEN DB |
| Keywords: | Ecrg4 | | glioma | | immunosurveillance | | microglia | | type-I IFN |
| Issue Date: | 2016 |
| Publisher: | Taylor & Francis |
| Journal Title: | Oncoimmunology |
| Volume: | 5 |
| Issue: | 12 |
| Start Page: | e1242547 |
| Publisher DOI: | 10.1080/2162402X.2016.1242547 |
| Abstract: | Esophageal cancer-related gene 4 (Ecrg4), a hormone-like peptide, is thought to be a tumor suppressor, however, little is known about the mechanism of how Ecrg4 suppresses tumorigenesis. Here, we show that the ecrg4 null glioma-initiating cell (GIC) line, which was generated from neural stem cells of ecrg4 knockout (KO) mice, effectively formed tumors in the brains of immunocompetent mice, whereas the transplanted ecrg4 wild type-GIC line GIC(+/+) was frequently eliminated. This was caused by host immune system including adaptive T cell responses, since depletion of CD4+, CD8+, or NK cells by specific antibodies in vivo recovered tumorigenicity of GIC(+/+). We demonstrate that Ecrg4 fragments, amino acid residues 71-132 and 133-148, which are produced by the proteolitic cleavage, induced the expression of pro-inflammatory cytokines in microglia in vitro. Moreover, blockades of type-I interferon (IFN) signaling in vivo, either depleting IFN-α/β receptor 1 or using stat1 KO mice, abrogated the Ecrg4-dependent antitumor activity. Together, our findings indicate a major antitumor function of Ecrg4 in enhancing host immunity via type-I IFN signaling, and suggest its potential as a clinical candidate for cancer immunotherapy. |
| Rights: | This is an Accepted Manuscript of an article published by Taylor & Francis in OncoImmunology in 2016, available online: http://www.tandfonline.com/10.1080/2162402X.2016.1242547 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/67736 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 森口 徹生
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