Tumor-Promoting Ly-6G+ SiglecFhigh Cells Are Mature and Long-Lived Neutrophils
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
Affiliations
Christina Pfirschke
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Camilla Engblom
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Jeremy Gungabeesoon
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Yunkang Lin
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Steffen Rickelt
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
Rapolas Zilionis
Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
Marius Messemaker
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Marie Siwicki
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Genevieve M. Gerhard
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Anna Kohl
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA
Etienne Meylan
Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Ralph Weissleder
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
Allon M. Klein
Department of Systems Biology, Harvard Medical School, Boston, MA, USA
Mikael J. Pittet
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Corresponding author
Summary: 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.
