Tumor-Promoting Ly-6G+ SiglecFhigh Cells Are Mature and Long-Lived Neutrophils

促肿瘤的Ly-6G+SiglecFhigh细胞是成熟且长寿命的中性粒细胞

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作者:Christina Pfirschke,Camilla Engblom,Jeremy Gungabeesoon,Yunkang Lin,Steffen Rickelt,Rapolas Zilionis,Marius Messemaker,Marie Siwicki,Genevieve M Gerhard,Anna Kohl,Etienne Meylan,Ralph Weissleder,Allon M Klein,Mikael J Pittet

Abstract

Myeloid cells co-expressing the markers CD11b, Ly-6G, and SiglecF can be found in large numbers in murine lung adenocarcinomas and accelerate cancer growth by fostering tumor cell invasion, angiogenesis, and immunosuppression; however, some of these cells' fundamental features remain unexplored. Here, we show that tumor-infiltrating CD11b+ Ly-6G+ SiglecFhigh cells are bona fide mature neutrophils and therefore differ from other myeloid cells, including SiglecFhigh eosinophils, SiglecFhigh macrophages, and CD11b+ Ly-6G+ myeloid-derived suppressor cells. We further show that SiglecFhigh neutrophils gradually accumulate in growing tumors, where they can live for several days; this lifespan is in marked contrast to that of their SiglecFlow counterparts and neutrophils in general, which live for several hours only. Together, these findings reveal distinct attributes for tumor-promoting SiglecFhigh neutrophils and help explain their deleterious accumulation in the tumor bed.

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