Recipient cells with susceptible NK-recognition profiles

Recipient cells with susceptible NK-recognition profiles refers to a cellular state, particularly in the context of allogeneic hematopoietic stem cell transplantation, where host cells lack specific inhibitory signals or express high levels of activating ligands that render them vulnerable to Natural Killer (NK) cell-mediated lysis. This concept is central to the "missing-self" hypothesis, which describes how NK cells identify and eliminate cells that fail to express adequate levels of Major Histocompatibility Complex (MHC) Class I molecules (Ljunggren & Kärre, 1990, Immunology Today). In clinical practice, a susceptible profile is often defined by a mismatch between the recipient's HLA ligands and the donor's inhibitory Killer-cell Immunoglobulin-like Receptors (KIRs), a condition that significantly enhances the graft-versus-leukemia (GvL) effect (Ruggeri et al., 2002, Science). Therapeutic strategies aim to exploit or induce this susceptibility by using monoclonal antibodies to block inhibitory checkpoints like KIR (e.g., lirilumab) or NKG2A (e.g., monalizumab), thereby lowering the threshold for NK cell activation against malignant targets (Shimasaki et al., 2020, Nature Reviews Drug Discovery). Additionally, the susceptibility profile can be modulated by drugs that upregulate stress-induced activating ligands, such as MICA or MICB, on the surface of tumor cells. While this profile is a descriptive cellular phenotype rather than a single molecular entity, it serves as a critical framework for donor selection in transplantation and the development of adoptive NK cell therapies for hematologic and solid malignancies (Velardi et al., 2012, Blood). Monitoring these profiles involves complex genetic typing and phenotypic assays to predict the efficacy and safety of NK-cell-based immunotherapies.

Other names

NK-cell susceptible targetsKIR-ligand mismatched recipient cellsMissing-self phenotype cellsNK-sensitive recipient cellsHLA-mismatched host cells

Enhancement of NK cell-mediated cytotoxicity through KIR blockade, NKG2A inhibition, IL-15 receptor agonism, or Antibody-Dependent Cellular Cytotoxicity (ADCC).