Natural killer cell-mediated tumor cell lysis (NK cell-mediated tumor lysis)

Natural killer cell-mediated tumor cell lysis is a key mechanism by which the immune system targets and destroys cancer cells without prior antigen exposure. NK cells recognize stressed, transformed, or infected cells through a repertoire of activating and inhibitory surface receptors. Activation leads to rapid cytotoxic responses, including the release of perforin and granzymes, direct engagement of death receptors (FasL/TRAIL), and antibody-dependent cytotoxicity (ADCC) via CD16. NK cell activation is modulated by cytokines (IL-2, IL-15, IL-18, IL-12), and effective surveillance is often compromised in the tumor microenvironment due to immunosuppressive cytokines (e.g., TGF-β, IL-10), regulatory cells, or downregulation of activating receptors. Therapeutic interventions include cytokine stimulation, monoclonal antibodies (to exploit ADCC), and engineered NK cells (e.g., CAR-NK). While potent, NK cell-based therapies present challenges including tumor immune evasion, regulatory cell-mediated inhibition, and safety in the context of toxicity and autoimmunity.

Other names

Tumor cell killing by NK cellsNK cell cytotoxicityNK cell antitumor activity

Activation of NK cells via cytokines (IL-2, IL-12, IL-15, IL-18) Engagement of activating receptors (NKG2D, NKp30, NKp44, NKp46) Death receptor pathway (Fas ligand/TRAIL inducing apoptosis in target cells) ADCC via CD16 (FcγRIIIA), enabling NK cell-mediated killing of antibody-coated tumor cells Release of cytolytic granules containing perforin and granzymes leading to target cell apoptosis