Additional NK Cell Pathways

KIR: regulates the first responders of immune defense

Killer cell Immunoglobulin-like Receptors (KIRs) are expressed on the surface of Natural Killer (NK) cells and are key regulators of their cytotoxic activity.¹ Data suggest that KIRs may also be expressed on cytotoxic T cells.²

Inhibitory KIRs are immune checkpoint receptors that stop NK cells from killing normal cells. Nearly every normal cell expresses the ligand for inhibitory KIRs.¹ When the ligand on the normal cell engages with the inhibitory KIR on the NK cell, the NK recognizes the cell as normal—and does not destroy it.¹

Tumor cells subvert this process in order to evade NK cell-mediated recognition and destruction. By upregulating the ligand for inhibitory KIRs, tumor cells disguise themselves as normal cells and escape detection by NK cells.³

In preclinical studies, blockade of inhibitory KIRs, however, has been shown to help restore NK cell-mediated immune activity.^4,5

Research to further understand these pathways is ongoing.

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References

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;105:251-258. 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.