Title: Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking.

Authors: Porrello, Alessandro; Leslie, Patrick L; Harrison, Emily B; Gorentla, Balachandra K; Kattula, Sravya; Ghosh, Subrata K; Azam, Salma H; Holtzhausen, Alisha; Chao, Yvonne L; Hayward, Michele C; Waugh, Trent A; Bae, Sanggyu; Godfrey, Virginia; Randell, Scott H; Oderup, Cecilia; Makowski, Liza; Weiss, Jared; Wilkerson, Matthew D; Hayes, D Neil; Earp, H Shelton; Baldwin, Albert S; Wolberg, Alisa S; Pecot, Chad V

Published In Nat Commun, (2018 May 18)

Abstract: 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.

PubMed ID: 29777108

MeSH Terms: No MeSH terms associated with this publication