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 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

View areas of research related to NLRP3

References

  1. Guarda G, Zenger M, Yazdi AS, et al. J Immunol. 2011;186(4):2529-2534.
  2. Dupaul-Chicoine J, Arabzadeh A, Dagenais M, et al. Immunity. 2015;43(4):751-763.
  3. Ghiringhelli F, Apetoh L, Tesniere A, et al. Nat Med. 2009;15(10):1170-1178.
  4. Shao B-Z, Xu Z-Q, Han B-Z, Su D-F, Liu C. Pharmacol. 2015;6:262. doi:10.3389/fphar.2015.00262.
  5. Embry CA, Franchi L, Nuñez G, Mitchell TC. Sci Signal. 2011;4(171):ra28. doi:10.1126/scisignal.2001486.
  6. Sharma D, Kanneganti T-D. J Cell Biol. 2016;213(6):617-629.
  7. Chow MT, Möller A, Smyth MJ. Semin Cancer Biol. 2012;22(1):23-32.
  8. He Y, Hara H, Núñez G. Trends Biochem Sci. 2016;41(12):1012-1021.
  9. Ben-Sasson SZ, Hogg A, Hu-Li J, et al. J Exp Med. 2013;210(3):491-502.
  10. Maltez VI, Tubbs AL, Cook KD, et al. Immunity. 2015;43(5):987-997.
  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.