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NLRP3
Nucleotide-binding oligomerization domain-like receptor family, pyrin domain- containing 3 (NLRP3) is involved in the assembly of the NLRP3 inflammasome, leading to enhanced antitumor response.
- NLRP3 is a protein expressed in antigen-presenting cells (APCs)
such as dendritic cells (DCs), monocytes, and macrophages1
- NLRP3 is involved in the assembly of the NLRP3 inflammasome, a key mediator of innate immunity and priming of T cells2,3
- NLRP3 expression is first induced by inflammatory signals4
- Specifically, NLRP3 expression and activation requires 2 separate inflammatory signals. Full activation of the inflammasome may be restricted to sites of inflammation, potentially avoiding damage to healthy cells5,6
- Factors released during tumor cell death, such as adenosine triphosphate (ATP), trigger assembly of the NLRP3 inflammasome, which then converts inactive IL-1β and IL-18 into their mature, active forms3,7,8
- These cytokines initiate APC priming as well as NK
- and cytotoxic
T-cell activation, leading to increased recruitment and antitumor function of these primary effector cells
2,3,9-12
- Preclinical studies suggest that the NLRP3 agonists can activate NK cells and initiate the priming of T cells, which promotes tumor inflammation and enhances antitumor function2,3,13
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REFERENCES–NLRP3
1. Guarda G, Zenger M, Yazdi AS, et al. Differential expression of NLRP3 among hematopoietic cells. J Immunol. 2011;186(4):2529-2534. 2. Dupaul-Chicoine J, Arabzadeh A, Dagenais M, et al. The Nlrp3 inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell tumoricidal activity. Immunity. 2015;43(4):751-763. 3. Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces