Stressed or altered tumor cells recognized by allogeneic NK cells

Stressed or altered tumor cells recognized by allogeneic NK cells refers to a physiological state of malignant cells characterized by the expression of stress-induced ligands and the loss of self-recognition markers. Natural Killer (NK) cells identify these targets through a balance of signals from activating receptors, such as NKG2D and Natural Cytotoxicity Receptors (NCRs), and inhibitory receptors like Killer-cell Immunoglobulin-like Receptors (KIRs) [1][2]. Malignant transformation often triggers the induced-self pathway, where cells upregulate ligands like MICA, MICB, and ULBPs in response to DNA damage, oxidative stress, or oncogenic signaling [3]. Simultaneously, many tumors downregulate Major Histocompatibility Complex (MHC) Class I molecules to evade T cells, which inadvertently triggers NK cell activation via the missing-self mechanism [4]. Therapeutic strategies targeting these cells involve the infusion of allogeneic NK cells, which are often pre-activated or genetically modified to enhance their natural affinity for these stressed cellular profiles and overcome immunosuppressive tumor microenvironments [2][5]. Sources: [1] Vivier E, et al. Science. 2011;331(6013):44-49; [2] Shimasaki N, et al. Nat Rev Drug Discov. 2020;19(3):200-218; [3] Raulet DH, et al. Nat Rev Immunol. 2013;13(10):705-717; [4] Ljunggren HG, Kärre K. Immunol Today. 1990;11(7):237-244; [5] Myers JA, Miller JS. Trends Cancer. 2021;7(6):528-539.

Other names

NKG2D ligand-expressing tumor cellsMHC-I deficient tumor cellsNK-sensitive malignant cellsInduced-self tumor cells

Allogeneic Natural Killer (NK) cells target these cells through a dual-signal system: the missing-self mechanism, where the absence of Major Histocompatibility Complex (MHC) Class I molecules prevents inhibitory signaling through Killer-cell Immunoglobulin-like Receptors (KIRs), and the induced-self mechanism, where activating receptors like NKG2D bind to stress-induced ligands (e.g., MICA/B) expressed on the tumor surface [1][2][4].