Natural killer cells in pancreatic cancer stroma

Figure 2 Activation and cytotoxicity of natural killer cells. Natural killer (NK) cells recognise a multitude of ligands on both healthy and transformed cells. Inhibitory receptors (red) recognise ‘self-antigens’ on healthy tissue preventing activation. However, these molecules are lost on aberrant cells as a result of viral transformation or malignancy (‘missing-self’) leading to NK cell activation. Alternatively, NK cells may become active through engagement of activating receptors (green) via stress ligands expressed on transformed cells. Binding of leukocyte function-associated antigen 1 to ICAM1 stabilises the immunological synapse between NK and target cells and ensures effective cytotoxicity. Upon activation NK cells release cytotoxic granules which contain perforin and granzymes to initiate target cell death via necrotic or apoptotic pathways. NK cells can also execute antibody dependent cellular cytotoxicity through Fc engagement of the CD16 receptor. Finally, NK cells secrete cytokines, such as interferon-γ, facilitating crosstalk between the adaptive and innate immune system, resulting in dendritic and T cell recruitment.