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Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12\u2010CXCR4 chemotaxis. These tumor\u2010infiltrating neutrophils express high level immunosuppressive molecules FasL and PD\u2010L2, and this FasL<jats:sup>+<\/jats:sup>PD\u2010L2<jats:sup>+<\/jats:sup> neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD\u2010L2 proteins with similar phenotype to those in GC tumors in both time\u2010dependent and dose\u2010dependent manners. Mechanistically, Th17 cell\u2010derived IL\u201017A and tumor cell\u2010derived G\u2010CSF can significantly induce neutrophil FasL and PD\u2010L2 expression via activating ERK\u2010NF\u2010<jats:italic>\u03ba<\/jats:italic>B and JAK\u2010STAT3 signaling pathway, respectively. Importantly, upon over\u2010expressing FasL and PD\u2010L2, neutrophils acquire immunosuppressive functions on tumor\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD\u2010L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL<jats:sup>+<\/jats:sup>PD\u2010L2<jats:sup>+<\/jats:sup> neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti\u2010cancer therapies targeting these pathogenic cells.<\/jats:p>","DOI":"10.1002\/advs.202103543","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T02:50:39Z","timestamp":1640573439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["FasL<sup>+<\/sup>PD\u2010L2<sup>+<\/sup> Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression"],"prefix":"10.1002","volume":"9","author":[{"given":"Zhi\u2010Guo","family":"Shan","sequence":"first","affiliation":[{"name":"Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery Southwest Hospital Third Military Medical University  Chongqing 400038 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