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 macrophages.1
  • NLRP3 is involved in the assembly of the NLRP3 inflammasome, a key mediator of innate immunity and priming of T cells.2,3
    • NLRP3 expression is first induced by inflammatory signals.4
      • 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 cells.5,6
  • 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 forms.3,7,8
  • 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 function.2,3,13

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  11. Freeman BE, Hammarlund E, Raué H-P, Slifka MK. Proc Natl Acad Sci U S A. 2012;109(25):9971-9976.
  12. Cooper MA, Fehniger TA, Ponnappan A, Mehta V, Wewers MD, Caligiuri MA. Eur J Immunol. 2001;31(3):792-801.
  13. Chow MT, Sceneay J, Paget C, et al. Cancer Res. 2012;72(22):5721-5732.