Journal article
NLRC4 suppresses melanoma tumor progression independently of inflammasome activation
The Journal of clinical investigation, Vol.126(10), pp.3917-3928
10/03/2016
DOI: 10.1172/JCI86953
PMCID: PMC5096827
PMID: 27617861
Abstract
Members of the NLR family can assemble inflammasome complexes with the adaptor protein ASC and caspase-1 that result in the activation of caspase-1 and the release of IL-1β and IL-18. Although the NLRC4 inflammasome is known to have a protective role in tumorigenesis, there is an increased appreciation for the inflammasome-independent actions of NLRC4. Here, we utilized a syngeneic subcutaneous murine model of B16F10 melanoma to explore the role of NLRC4 in tumor suppression. We found that NLRC4-deficient mice exhibited enhanced tumor growth that was independent of the inflammasome components ASC and caspase-1.
Nlrc4
expression was critical for cytokine and chemokine production in tumor-associated macrophages and was necessary for the generation of protective IFN-γ–producing CD4
+
and CD8
+
T cells. Tumor progression was diminished when WT or caspase-1–deficient, but not NLRC4-deficient, macrophages were coinjected with B16F10 tumor cells in NLRC4-deficient mice. Finally, examination of human primary melanomas revealed the extensive presence of NLRC4
+
tumor-associated macrophages. In contrast, there was a paucity of NLRC4
+
tumor-associated macrophages observed in human metastatic melanoma, supporting the concept that NLRC4 expression controls tumor growth. These results reveal a critical role for NLRC4 in suppressing tumor growth in an inflammasome-independent manner.
Details
- Title: Subtitle
- NLRC4 suppresses melanoma tumor progression independently of inflammasome activation
- Creators
- Ann M Janowski - Inflammation Program andOscar R Colegio - Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USAEmma E Hornick - Inflammation Program andJennifer M McNiff - Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USAMatthew D Martin - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa, USAVladimir P Badovinac - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa, USALyse A Norian - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USAWeizhou Zhang - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa, USASuzanne L Cassel - Inflammation Program andFayyaz S Sutterwala - Inflammation Program and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.126(10), pp.3917-3928
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI86953
- PMID
- 27617861
- PMCID
- PMC5096827
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/03/2016
- Academic Unit
- Microbiology and Immunology; Pathology; Radiation Oncology
- Record Identifier
- 9984083267802771
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