Additional NK Cell Pathways
- PD-1 Pathway
- CTLA-4 Pathway
- Additional Effector T Cell
- SLAMF7 Pathway
- Additional NK Cell
- Non-effector Cell
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.
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.