Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation

Mana Taki, Kaoru Abiko (), Tsukasa Baba, Junzo Hamanishi, Ken Yamaguchi, Ryusuke Murakami, Koji Yamanoi, Naoki Horikawa, Yuko Hosoe, Eijiro Nakamura, Aiko Sugiyama, Masaki Mandai, Ikuo Konishi and Noriomi Matsumura
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Mana Taki: Kyoto University Graduate School of Medicine
Kaoru Abiko: Kyoto University Graduate School of Medicine
Tsukasa Baba: Kyoto University Graduate School of Medicine
Junzo Hamanishi: Kyoto University Graduate School of Medicine
Ken Yamaguchi: Kyoto University Graduate School of Medicine
Ryusuke Murakami: Kyoto University Graduate School of Medicine
Koji Yamanoi: Kyoto University Graduate School of Medicine
Naoki Horikawa: Kyoto University Graduate School of Medicine
Yuko Hosoe: Kyoto University Graduate School of Medicine
Eijiro Nakamura: Kyoto University Graduate School of Medicine
Aiko Sugiyama: Kyoto University Graduate School of Medicine
Masaki Mandai: Kyoto University Graduate School of Medicine
Ikuo Konishi: Kyoto University Graduate School of Medicine
Noriomi Matsumura: Kyoto University Graduate School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.

Date: 2018
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DOI: 10.1038/s41467-018-03966-7

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