Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells

Publication date: 14 December 2015
Source:Cancer Cell, Volume 28, Issue 6
Author(s): Adam Blaisdell, Amandine Crequer, Devin Columbus, Takiko Daikoku, Khush Mittal, Sudhansu K. Dey, Adrian Erlebacher
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.

Graphical abstract

Teaser

Blaisdell et al. show in a mouse model of uterine cancer that polymorphonuclear neutrophil (PMN) recruitment resulting from tumor hypoxia impedes early tumor growth and malignant progression. A PMN gene signature correlates with improved survival in multiple human cancer types.


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