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KIR

KIR pathway expressed on NK cells diagram

Killer cell immunoglobulin-like receptor (KIR), an immune checkpoint receptor expressed on natural killer (NK) cells, may inhibit NK cells from destroying normal cells. Inhibition of KIR may enhance NK cell antitumor activity.

  • KIRs are inhibitory immune checkpoint receptors expressed on NK cells and cytotoxic T cells1,2
    • Nearly every normal cell expresses the ligand for inhibitory KIRs1
  • KIRs are key regulators of NK-cell cytotoxic activity1
    • When the ligand on the normal cell engages with the inhibitory KIR on the NK cell, the NK cell recognizes the cell as normal and does not destroy it1
  • In preclinical studies, blockade of inhibitory KIRs has been shown to help restore NK cell–mediated immune activity4,5
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REFERENCES–KIR

1. Campbell KS, Purdy AK. Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011;132(3):315-325. 2. Björkström NK, Béziat V, Cichocki F, et al. CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells. Blood. 2012;120(17):3455-3465. 3. Carbone E, Neri P, Mesuraca M, et al. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood. 2005;105(1):251-258. 4. Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27(45):5932-5943. 5. Romagné F, André P, Spee A, et al. Preclinical characterization of 1-7F9, a novel human anti–KIR receptor therapeutic antibody that augments natural killer–mediated killing of tumor cells. Blood. 2009;114(13):2667-2677.