Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Jonathan Cools-Lartigue,Jonathan Spicer,Braedon McDonald,Stephen Gowing,Simon C. Chow,Betty Giannias,Paul Kubes,Lorenzo E. Ferri +7 more
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TLDR
It is reported that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions and NETs are identified as potential therapeutic targets in the context of systemic infection.Abstract:
The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.read more
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Posted ContentDOI
Gram-negative bacterial infection increases lung cancer metastasis via Toll-like receptor 1 activation and increased cancer cell proliferation post-tumor adhesion
Roni F. Rayes,M. G. Wilson,Stephen Gowing,F. Bourdeau,Betty Giannias,Sophie Camilleri-Broët,Pierre-Olivier Fiset,Sara Najmeh,Jonathan Spicer,Lorenzo E. Ferri,Jonathan Cools-Lartigue +10 more
TL;DR: In this paper, the TLR4-initiated host response to gram negative infection post-tumor cell adhesion was found to be responsible for lung cancer metastasis.
Patent
NNIF and nNIF-related peptides and related methods
TL;DR: Neonatal NET-Inhibitory Factor (nNIF) and nNIF-Related Peptides (NRPs) are provided in this paper for the treatment of and prophylaxis against inflammatory disorders and cancer.
Journal ArticleDOI
ENPP1 Immunobiology as a Therapeutic Target
TL;DR: A comprehensive review of ENPP1 inhibitors can be found in this paper , which summarizes the current state of the art and opens new perspectives for novel treatment strategies, such as immune-checkpoint blockade, STING activation, DNA damage response (DDR) inhibitors, and radiotherapy (RT).
Book ChapterDOI
The Intersection of Biomaterials, Tissue Engineering, and Immuno-oncology
TL;DR: In this article , the authors examine advances in 3D biomaterials and tissue engineering strategies used to expand our understanding of tumor-immune interactions, and how engineered platforms are being applied toward immunotherapy development.
Journal ArticleDOI
Casting a Wide NET
TL;DR: This Pillars of Immunology article is a commentary on “Neutrophil extracellular traps kill bacteria,” a pivotal article written by V. Brinkmann and A. Weinrauch in 2004 and published in Science, in 2004.
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