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Cancer Cell. 2015 Dec 14;28(6):785-799. doi: 10.1016/j.ccell.2015.11.005.

Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.

Author information

1
Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
2
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
3
Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; NYU Cancer Institute, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address: adrian.erlebacher@nyumc.org.

Abstract

Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the basement membrane, PMNs impeded early-stage tumor growth and retarded malignant progression. Unexpectedly, PMN recruitment and tumor growth control occurred independently of lymphocytes and cellular senescence and instead ensued as part of the tumor's intrinsic inflammatory response to hypoxia. In humans, a PMN gene signature correlated with improved survival in several cancer subtypes, including PTEN-deficient uterine cancer. These findings provide insight into tumor-associated PMNs and reveal a context-specific capacity for PMNs to directly combat tumorigenesis.

PMID:
26678340
PMCID:
PMC4698345
DOI:
10.1016/j.ccell.2015.11.005
[Indexed for MEDLINE]
Free PMC Article

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