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

doi:10.1016/j.celrep.2020.108164

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

Cell Rep. 2020 Sep 22;32(12):108164. doi: 10.1016/j.celrep.2020.108164.

Affiliations

¹ Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.
² David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
⁴ Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
⁵ 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.
⁶ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁷ 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. Electronic address: mikael.pittet@unige.ch.

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⁺ 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.

Keywords: cancer; myeloid cells; neutrophils.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung / metabolism*
Adenocarcinoma of Lung / pathology*
Animals
Antigens, Ly / metabolism*
Cell Line, Tumor
Cell Proliferation
Lung / pathology
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Male
Mice, Inbred C57BL
Neutrophils / pathology*
Sialic Acid Binding Immunoglobulin-like Lectins / metabolism*

Substances

Antigens, Ly
Ly6G antigen, mouse
Sialic Acid Binding Immunoglobulin-like Lectins
Siglecf protein, mouse