Tumor cells recognized and lysed by allogeneic activated NK cells

This entry refers to the susceptibility of malignant cells to the cytotoxic activity of donor-derived (allogeneic) natural killer (NK) cells. NK cells are innate lymphocytes that identify transformed cells through a complex integration of signals from activating receptors (such as NKG2D and natural cytotoxicity receptors) and inhibitory receptors (such as Killer-cell Immunoglobulin-like Receptors, or KIRs) (Vivier et al., Science, 2011). In the allogeneic setting, NK cells can be particularly effective if the donor's inhibitory KIRs do not recognize the Human Leukocyte Antigens (HLA) on the patient's tumor cells, a phenomenon known as KIR-HLA mismatch or the 'missing self' hypothesis (Ruggeri et al., Science, 2002). Upon recognition, activated NK cells release cytotoxic granules containing perforin and granzymes, leading to the rapid lysis of the target tumor cell. This mechanism forms the basis for various adoptive cellular immunotherapies currently in clinical development for both hematologic and solid malignancies (Shimasaki et al., Nature Reviews Drug Discovery, 2020). Because this entry describes a cellular interaction and a phenotypic outcome rather than a single molecular entity, it is classified as a cellular target rather than a traditional pharmacological receptor.

Other names

Allogeneic NK cell-mediated cytotoxicityNK cell-sensitive tumor cellsAdoptive NK cell therapy targetsKIR-mismatched tumor targets

Allogeneic NK cells utilize a repertoire of activating receptors (e.g., NKG2D, DNAM-1) to recognize stress-induced ligands on tumor cells and trigger perforin/granzyme-mediated lysis, often benefiting from KIR-HLA mismatch to bypass inhibitory signaling (Ruggeri et al., Science, 2002).