Multiple Natural Killer cell surface receptors and effector mechanisms (NK cell receptors)

Natural Killer (NK) cells are essential components of the innate immune system, specialized in identifying and destroying stressed, infected, or neoplastic cells without prior sensitization. Their function is governed by a sophisticated balance of signals from a diverse array of germline-encoded surface receptors, categorized into activating (e.g., NKG2D, NKp46) and inhibitory (e.g., KIRs, NKG2A) types [3]. Effector mechanisms involve the directed release of perforin and granzymes to induce apoptosis, as well as the production of cytokines like interferon-gamma to orchestrate broader immune responses [4]. In the context of oncology, many tumors evade NK cell surveillance by upregulating ligands for inhibitory receptors, leading to a state of exhaustion or suppression. Therapeutic interventions, such as monoclonal antibodies like monalizumab (targeting NKG2A) or lirilumab (targeting KIRs), aim to disrupt these inhibitory signals and restore the NK cells' potent anti-tumor effector functions [1, 2]. Additionally, NK cells mediate antibody-dependent cellular cytotoxicity (ADCC) through the CD16 receptor, which is a key mechanism for many established therapeutic antibodies [4]. Citations: [1] André, P., et al. (2018). Cell. [2] Vey, N., et al. (2012). Blood. [3] Vivier, E., et al. (2011). Science. [4] Long, E. O., et al. (2013). Annual Review of Immunology.

Other names

NK cell activating receptorsNK cell inhibitory receptorsNK cell checkpointsNK cell effector pathwaysNatural Killer cell receptors

Modulation of Natural Killer cell activity through the blockade of inhibitory receptors (checkpoints) or the stimulation of activating receptors to enhance anti-tumor or anti-viral cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC).