NK Cell-Mediated Cytotoxicity

Natural killer (NK) cells are defined as large granular lymphocytes and play a critical role in the innate immune system. They often lack antigen-specific cell surface receptors. Instead of acting via antigen-specific receptors, like T-cells, lysis of tumor cells by NK cells involves exocytosis of cytoplasmic granules from the NK cell towards cancer cells; this process can directly occur in the proximity of cancer cells or after engagement of alternative receptor members of the TNF superfamily (FasL/TNF) and their corresponding ligands (Fas/TNFR).

NK cell mediated lysis of cancer cells

NK cells can mediate cancer cell killing through the release of granules/granzymes. This occurs:

  1. in a direct manner or after activation of receptors on the NK cell's surface that bind ligands on the cancer cell's surface.
  2. Upon this activation, the cytotoxic granules released by the NK cells are vectorially secreted into the intercellular space formed during conjugation of the NK cell and the cancer cell.
  3. The granules contain a number of proteins, including perforin, that induce the formation of membrane lesions on the cancer cell, resulting in NK cell mediated lysis of cancer cells.


Janeway, C. et al. Immunobiology. The immune system in health and disease. 6th Edition.

Zhu, Y. et al. Fas ligand and lytic granule differentially control cytotoxic dynamics of natural killer cell against cancer target. Oncotarget. Jul 2016; Vol. 7, Issue 30, pp 47163-47172

Chester, C. et al. Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy. Front. Immunol., 02 Dec 2015

Borrego, F. et al. Editorial: NK Cell-Based Cancer Immunotherapy. Front Immunol. Jun 2016, Vol. 27; Issue 7, pp 249