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Janowski, A. M., Colegio, O. R., & Hornick, E. E. (2016). NLRC4 suppresses melanoma tumor progression independently of inflammasome activation. The Journal of Clinical Investigation, 126(10), 3917–3928. Added by: Dr. Enrique Feoli (02/05/2023, 18:16) Last edited by: Dr. Enrique Feoli (02/05/2023, 18:17) |
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| Resource type: Journal Article DOI: 10.1172/JCI86953 BibTeX citation key: Janowski2016 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Ageing Creators: Colegio, Hornick, Janowski Collection: The Journal of Clinical Investigation |
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| Abstract |
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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.
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| Notes |
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Publisher: The American Society for Clinical Investigation
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