Factor XIIIA—expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking

• DOI: 10.1038/s41467-018-04355-w
• Publication Date: 2018-05-14T10:54:27Z
• Authors: Alessandro Porrello; Patrick L. Leslie; Emily B. Harrison; Balachandra K. Go...; Sravya Kattula; Subrata K. Ghosh; Salma H. Azam; Alisha Holtzhausen; Yvonne L. Chao; Michele C. Hayward; Trent A. Waugh; Sanggyu Bae; Virginia Godfrey; Scott H. Randell; Cecilia Oderup; Liza Makowski; Jared Weiss; Matthew D. Wilkerson; D. Neil Hayes; H. Shelton Earp; Albert S. Baldwin; Alisa S. Wolberg; Chad V. Pecot
• Keywords: Factor XIIIa

Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% cases. Molecular aberrations in adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances LUSC not materialized. However, immune checkpoint inhibitors sub-populations patients led to exciting responses. Using computational analyses The Cancer Genome Atlas, we identified a subset tumors characterized by dense infiltration inflammatory monocytes (IMs) poor survival. With novel, immunocompetent metastasis models, demonstrated that tumor cell derived CCL2-mediated recruitment IMs necessary sufficient metastasis. Pharmacologic inhibition IM had substantial anti-metastatic effects. Notably, show highly express Factor XIIIA, which promotes fibrin cross-linking create scaffold invasion metastases. Consistently, human samples containing extensive cross-linked microenvironment correlated with