By: Dana Abdel Hafeez
Natural killer cells (NK cells) are a class of lymphocytes and an important component of the innate immune system (1). They play a primary role in the spontaneous killing of allogeneic (nonself) and autologous (patient’s own) cells (1). NK cells are activated and controlled by a dynamic equilibrium between antagonistic and complementary pathways which come about through an interaction with target cells (1). The NK cells encompass a variety of activation cell surface receptors, in particular, the NKG2D receptor is responsible for detecting target cells (2). NK cells store cytotoxic proteins inside of secretory lysosomes which are particular exocytic organelles (2). The moment that a target cell is recognized by the NKG2D receptor, it activates a polarized exocytosis function of NK cells to eliminate the cell by releasing the secretory lysosomes (3). These molecules have degradative functions and utilize cytotoxic proteins (granzymes and perforin) which help eliminate target cells (2,4). Perforin facilitates the admission of granzymes, proteases that work to induce apoptosis, into the target cell cytoplasm (4). The exocytosis of secretory lysosomes is a highly ordered process to ensure that NK cells do not kill indiscriminately (3). NK cells possess the ability to bind to tumour-bound immunoglobulin G antibodies which is an essential aspect in anticancer therapy through the use of NK cells (5). Research conducted at McMaster University notes that since dendritic cell (DC) based vaccines have only achieved mediocre success in clinical trials, further enhancement of DC vaccines paired with NK cell mediation is required (6). The prospect role of NK cells in vaccination therapy is important in the battle of DC vaccine improvement as the antigen specific properties are essential in locating target cells (6). In current research being conducted by McMaster University, it is portrayed how the mechanisms used by NK cells to kill tumour cells compliment the activity of DC cell function. The release of tumor associated antigens followed by NK-mediated lysis can facilitate vaccine specific priming and responses by inducing epitope spreading (6). The protocol that is used to induce DC maturation is shown to impact the extent to which tumoricidal NK cells are activated (6). Further research is being conducted to demonstrate how NK cells and DC can be coupled in their mechanisms to produce higher achieving vaccinations that can be carried over to a clinical setting (6).
References
1. Vivier E. Natural Killer Cell Signaling Pathways. Science. 2004;306(5701):1517-1519. Available from:http://science.sciencemag.org/content/306/5701/1517 [Accessed 10thFebruary 2019]
2. Bauer S. Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA. Science. 2014;285(5428):727-729. Available from:http://science.sciencemag.org/content/285/5428/727?casa_token=D5mW89V2vbQAAAAA:hko8OhjLpdrnJPSyzUj_GIeWEZn1irDQCq1NiAwI_cRL4Qbte4pFzKBT9BBAxiXJ2BDADho3DTK9gWM[Accessed 11thFebruary 2019]
3. Topham N, Hewitt E. Natural killer cell cytotoxicity: how do they pull the trigger?. Immunology. 2009;128(1):7-15. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747134/ [Accessed 10thFebruary 2019]
4. Altmann D. Natural killer cell transcriptional control, subsets, receptors and effector function. Immunology. 2019;156(2):109-110. Available from:https://onlinelibrary.wiley.com/doi/full/10.1111/imm.13041[Accessed 11thFebruary 2019]
5. Dahlberg C, Sarhan D, Chrobok M, Duru A, Alici E. Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity. Frontiers in Immunology. 2015;6. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663254/[Accessed 12thFebruary 2019]
6. Bourdreau J. Manipulating dendritic cells for activation of tumoricidal natural killer cells. ProQuest Dissertations Publishing,. 2011;(McMaster University).
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