Acute myeloid leukemia cells via multi-receptor NK cell immune recognition

Natural Killer (NK) cells recognize Acute Myeloid Leukemia (AML) cells through a sophisticated balance of activating and inhibitory signals (PMID: 30613051). Key activating receptors involved in this multi-receptor recognition include NKG2D, which binds to MICA/B and ULBP ligands, and DNAM-1 (CD226), which interacts with CD112 and CD155 on the surface of AML blasts (PMID: 28614739). This immune recognition is often triggered by the missing-self hypothesis, where the downregulation of MHC class I molecules on leukemia cells removes inhibitory signals to the NK cell (Nature Reviews Cancer, 2019). Therapeutic interventions, such as Tri-specific Killer Engagers (TriKEs) like GTB-3550, are designed to enhance this multi-receptor engagement by simultaneously targeting CD16 on NK cells and CD33 on AML cells while providing IL-15 stimulation (ClinicalTrials.gov NCT03214666). This approach aims to overcome the immune evasion tactics employed by AML cells, such as the shedding of activating ligands or the upregulation of checkpoint molecules like TIGIT.

Other names

NK cell-mediated AML recognitionMulti-receptor NK cell activation against AMLNK cell immune surveillance of AML

Induction of NK cell cytotoxicity against AML blasts through the simultaneous engagement of multiple activating receptors (e.g., NKG2D, DNAM-1, NKp46) and the recognition of missing-self signals due to MHC class I downregulation.