Tumor-Promoting Ly-6G(+) SiglecF(high) Cells Are Mature and Long-Lived Neutrophils

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

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(+) SiglecF(high) cells are bona fide mature neutrophils and therefore differ from other myeloid cells, including SiglecF(high) eosinophils, SiglecF(high) macrophages, and CD11b(+) Ly-6G(+) myeloid-derived suppressor cells. We further show that SiglecF(high) neutrophils gradually accumulate in growing tumors, where they can live for several days; this lifespan is in marked contrast to that of their SiglecF(low) counterparts and neutrophils in general, which live for several hours only. Together, these findings reveal distinct attributes for tumor-promoting SiglecF(high) neutrophils and help explain their deleterious accumulation in the tumor bed.