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. 2022 Sep 5;12:989167. doi: 10.3389/fonc.2022.989167

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Copyright © 2022 Zhang, Xu, Xu and Ye

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The graphic abstract in this study. By using a compound library, we identified a natural compound IVM, which significantly suppressed CTSBinduced NETs. The precise mechanism of IVM was targeting GSDMD and significantly suppressed GSDMD oligomerization. Thus IVM suppressed GSDMD-dependent NETs. The formation of NETs significantly promotes melanoma cancer metastasis through increasing TGF-b, MMP9 and myeloid-derived suppressor cells and suppressed CD8+T cells activation.