Susceptible tumor cells engaged by TGF-beta-imprinted universal donor NK cells

This entry describes a complex biological interaction rather than a single molecular target or receptor. It refers to the process by which malignant cells are recognized and eliminated by a specialized class of Natural Killer (NK) cells that have been 'imprinted' with Transforming Growth Factor-beta (TGF-beta) during their expansion or differentiation. While TGF-beta is typically an immunosuppressive cytokine in the tumor microenvironment, ex vivo imprinting (often in combination with cytokines like IL-12, IL-15, and IL-18) programs these NK cells into a 'memory-like' state with enhanced metabolic fitness, increased persistence, and resistance to TGF-beta-mediated inhibition. These 'universal donor' NK cells are typically derived from induced pluripotent stem cells (iPSCs) or healthy donor cord blood and are engineered to be 'off-the-shelf' therapies. The 'target' in this context is the population of tumor cells expressing ligands for NK activating receptors, such as MICA/B and ULBPs, which trigger the NK cells' cytotoxic machinery upon engagement.

Other names

Tumor cells targeted by TGFβi NK cellsTGF-beta-imprinted NK cell targetsMalignant cells susceptible to imprinted NK cytotoxicity

Direct cellular cytotoxicity mediated by the engagement of NK cell activating receptors (e.g., NKG2D, NKp46, DNAM-1) with their respective ligands on tumor cells, leading to the release of perforin and granzymes.