The future is now: The Natural Killer cells

The immune system plays a pivotal role in the protection of the human body against various kinds of diseases, infection or defective immune system itself. Since defective cells are the body’s very own cells, conditions that are associated with mutated cells may not be completely detected and destructed by the immune system. Cancer cells and other variants of cell mutations also have the ability to evade or undermine an immunologic response. Thus, the recent emergence of immunotherapy has paved a new road into the treatment of these chronic diseases and malignancies. Immunotherapy is designed to enhance the immune system to more effectively detect and combat the abnormal cells. It has also shown enhanced-effects when applied together with medical, radiotherapeutical, chemotherapeutical as well as surgical treatments. Like other forms of treatment, it consists of many types, but mainly divided into two major constituents: those that act directly against the mutated or defective cells, and; those that act directly to enhance the immune system. One of the most widely-discussed subtypes of immunotherapy is none other than the “Natural Killer” or NK Cell Therapy. The discovery of NK cells was first addressed in the early 1970s by Dr. Ronald Herberman and his team.

Natural Killer cells are known to be the first-line of defence against foreign, damaged, infected or malignant cells. As their name implies, NK cells eliminate cells that are prone to pose dangers upon the host’s immune system; hence, are deemed to be the key regulators in immunosurveillance, transplantation rejection reaction, and early immune response against viruses. NK cells are able to differentiate between healthy and mutated cells mainly via their surface receptors. Additionally, they typically kill the foreign or mutated cells through the secretion of special enzymes (i.e. Granzyme B and perforin), as well as induction of specific cellular pathways directly leading to the death of their targeted cells. They can also release specific immunologic substances, medically-referred to as the “pro-inflammatory cytokines”, that exhibit direct anti-tumoral response, along with activation of specific immunologic reaction within the host. Hence, these cells do not exhibit their functions only through direct elimination of malignant or virally-transformed cells, but also through their positive or negative immunomodulation (change in body’s immune system) on T cells, a subtype of white blood cell.

However, the level of activities of NK cells in cancer patients are susceptible to be down regulated depending on many conditions. Patients with autoimmune diseases were also found to have lower level of circulating NK cells as compared to their healthy counterparts. Thus, it can be concluded that in the presence of circulating tumoral cells or for those with autoimmune diseases, NK cell numbers and activities may not be at their optimal level and function. Since NK cells may hold the secret behind the treatment of malignancies and autoimmune diseases, harnessing NK cells and culturing them may serve as an appealing therapeutic option. Natural killer cells can be harnessed from different sources, either from the patients themselves or from healthy donors. Since the numbers in the circulation are typically very low in each individual and most of the circulating ones are the naive or “inexperienced” NK cells, they are usually collected for culture and are required to undergo “the so-called special training” prior to being administered back to the patients as a
“full-fledged, adult NK soldiers”. Immunotherapy has heretofore been encircling around T cells, but NK cells are now being given more attention due to them being more rapidly responsive. Amazingly, NK cells have also been reported to be able to recall past exposures.

Many studies have also unveiled that patients with higher circulating numbers of NK and T cells have a better prognosis as compared to those with lower circulating numbers. NK cells are found to be more reactive in patients with haematological (blood-related) cancers or metastases due to the slightly more extensive presence in the circulatory system. On the contrary, solid forms of tumours are comparatively scarce of NK cell population as a result of cancer immune-modulating ability, causing them to be functionally less active. The most recent successful story of NK cells administration in Thailand was reported by the doctors from King Chulalongkorn Memorial Hospital, where five patients with leukaemia received positive results after the application of NK cells. Immunomodulatory drugs such as Thalidomide also have the ability to enhance the “killing” abilities of NK cells. Immunotherapy is becoming more widely-accepted in the medical world due to its potency and ability to specifically target abnormal cells. Among the many variants of immunotherapeutic options, NK cells show a promising role since they are the front-liners of the white blood cell army. Though, culturing and “training” them are still of a great challenge due to the relatively low circulating levels in the human blood, many medical institutions are starting to utilise NK cell therapy as part of their treatment regimens, while a few others have already obtained successful results following their applications.

Reference
Pahl, J., & Cerwenka, A. (2017). Tricking the balance: NK cells in anti-cancer immunity. Immunobiology.https://doi.org/10.1016/j.imbio.2015.07.012
Guillerey, C., Huntington, N. D., & Smyth, M. J. (2016). Targeting natural killer cells in cancer immunotherapy. Nature Immunology. https://doi.org/10.1038/ni.3518
Schleinitz, N., Vély, F., Harlé, J. R., & Vivier, E. (2010). Natural killer cells in human autoimmune diseases. Immunology. https://doi.org/10.1111/j.1365-2567.2010.03360.x

Thiti Samutharat, MD
Verita Life, Integrative Cancer Centre
www.veritalife.com
+66 2 554 8333
[email protected]