期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-04355-w
关键词
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资金
- NCI [2-P30-CA016086-40, CA180134]
- NIEHS [2-P30ES010126-15A1]
- UCRF
- NCBT [2015-IDG-1007]
- National Institutes of Health [R01CA215075]
- American Cancer Society [MRSG-14-222-01-RMC]
- Jimmy V Foundation Scholar award
- UCRF Innovator Award
- Stuart Scott V Foundation/Lung Cancer Initiative Award for Clinical Research
- University Cancer Research Fund
- Lung Cancer Research Foundation
- Free to Breathe Metastasis Research Award
- Susan G. Komen Career Catalyst Award
- National Institute of General Medical Sciences [5T32 GM007092]
- National Cancer Institute of the National Institutes of Health [T32CA196589]
- NIH [P30DK065988, R35CA197684, R01HL126974, F31HL139100]
- NCI Center Core Support Grant [CA016086]
- North Carolina Biotech Center Institutional Support Grant [2012-IDG-1006]
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival. With novel, immunocompetent metastasis models, we demonstrated that tumor cell derived CCL2-mediated recruitment of IMs is necessary and sufficient for LUSC metastasis. Pharmacologic inhibition of IM recruitment had substantial anti-metastatic effects. Notably, we show that IMs highly express Factor XIIIA, which promotes fibrin cross-linking to create a scaffold for LUSC cell invasion and metastases. Consistently, human LUSC samples containing extensive cross-linked fibrin in the microenvironment correlated with poor survival.
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