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

Cell Reports (Sep 2020)

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

Journal volume & issue: Vol. 32, no. 12
p. 108164

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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