Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells

被引:135
作者
Blaisdell, Adam [1 ]
Crequer, Amandine [1 ]
Columbus, Devin [1 ]
Daikoku, Takiko [2 ]
Mittal, Khush [1 ]
Dey, Sudhansu K. [2 ]
Erlebacher, Adrian [1 ,3 ]
机构
[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[2] Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH 45229 USA
[3] NYU Langone Med Ctr, NYU Canc Inst, New York, NY 10016 USA
关键词
ENDOMETRIAL CANCER; ANTITUMOR IMMUNITY; IN-VIVO; INFLAMMATION; SENESCENCE; MICE; TUMORIGENESIS; CXCR2; LUNG; SUPPRESSION;
D O I
10.1016/j.ccell.2015.11.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:785 / 799
页数:15
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