Journal
IMMUNITY
Volume 43, Issue 4, Pages 751-763Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2015.08.013
Keywords
-
Categories
Funding
- Canadian Institutes for Health Research (CIHR-MOP) [82801, 86582]
- Burroughs Wellcome Fund
- CIHR
- FRSQ
- Strauss Foundation
- CIHR/CAG/Abbott fellowship
- American Cancer Society [PF-11-152-01-LIB]
Ask authors/readers for more resources
The crosstalk between inflammation and tumorigenesis is now clearly established. However, how inflammation is elicited in the metastatic environment and the corresponding contribution of innate immunity pathways in suppressing tumor growth at secondary sites are poorly understood. Here, we show that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired inteleukin- 18 (IL-18) signaling. Control of tumor growth was independent of differential cancer cell colonization or proliferation, intestinal microbiota effects, or tumoricidal activity by the adaptive immune system. Instead, the inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of the death ligand FasL, and capacity to kill FasL-sensitive tumors. Our results define a regulatory signaling circuit within the innate immune system linking inflammasome activation to effective NK-cell-mediated tumor attack required to suppress colorectal cancer growth in the liver.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available