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RECENT RESEARCH: Reduction in Natural Killer Cells May Increase Virus-Induced Cancer Risk

Periodically, we like to share groundbreaking research to update our audience on current cancer research as it relates to virus-induced cancers. Today we’re discussing new research on the role that Natural Killer (NK) cells may play in preventing cancer.

Artistic illustration of natural killer cells attacking a cancerous cell.

While the name Natural Killer (NK) Cells may seem foreboding, these white blood cells are integral in the fight against viruses, cancers, and virus-induced cancers. NK cells comprise 5-15% of all lymphocytes, a subset of a white blood cells known to:


  1. Detect foreign, potentially-dangerous proteins,

  2. Initiate our body’s defense mechanisms, and

  3. Destroy viral cells. (1)


By destroying the foreign cell’s encasing known as the membrane, NK cells are able to induce a programmed cell death (apoptosis) in infected cells. After NK cells destroy invading cells, they take a distinctive structure from the outside surface of the invading cell known as the antigen and present it to the immune system. The immune system will then process the structure and composition of the antigen to create a specific guard against this type of viral protein. Therefore, the next time the viral protein is detected, these defense cells will be quickly activated to destroy the dangerous pathogen. (1) While it has long been clear how these NK cells provide important defense mechanisms, only recently have scientists began to understand the extent to which these NK cells contribute to preventing virus-induced cancer formation. Current research is taking a deeper dive into the precise mechanism NK cells employ to hinder the spread of virus-induced cancers, directed toward eventually developing an NK cell-based cancer treatment. (2)


Medical literature has revealed that Natural Killer Cell Deficiency (NKD) leads to a decrease in cancer immunity related to two general concepts:


  1. Poor tumor cell removal

  2. Increased risk of cancer cell spreading (metastasis).


A recent article published (Front. Immunol. 2019, doi: 10.3389/fimmu.2019.01703) by Won Moon and Simon Powis reviews ten clinical studies that discuss NKD and virus-induced dangers associated with NKD patients’ compromised immune functions. The ultimate goal of this study is to find the underlying mechanism of cancer development. (3)


Moon and Powis’ study particularly focuses on the Epstein-Barr virus (EBV) and the Human papillomavirus (HPV) as leading causes of NKD-associated, virus-induced cancers in the body. EBV and HPV are fairly common viruses (as shown in Table 1 below). With such a high volume of people with EBV/HPV, many of these people will develop virus-induced cancers, so it is important to expand our knowledge of this field.


Table 1: Approximate Incidence of EBV and HPV and Associative Cancers in the General Population (4-7)


Those with NKD have a reduced number of effective NK cells able to protect against foreign material, including both viruses (such as EBV/HPV) and tumor cells. This condition is caused by mutations in particular regions of the DNA sequence, which subsequently leads to improper formation of the NK cells. With fewer working NK cells able to fight potentially harmful pathogens, more viral and tumor cells are able to avoid destruction. Therefore, this condition allows more viruses and cancers to spread throughout the body, infect normal cell tissues, and cause life-threatening issues. (3,8)


In one example presented in the study, HPV-16, a common strain of HPV, plays a role in inhibiting the proper function of NK cells. Without properly functioning NK cells, HPV-16 is able to drive cervical cancer growth. Although the cancer-producing pathway remains somewhat unclear, this case provides evidence of the viral effects associated with diminished NK cell function. Another patient with NKD developed latent EBV. In infected tissues, the patient’s normal cell machinery had been hijacked by the viral cell DNA. The EBV virus was then able to use the normal cell’s replication process in order to proliferate quickly. With increasing viral infection, more mutations occur, which facilitate possible cancer development. Other studies provide similar examples on the relationship between NKD causing EBV and HPV, which in turn lead to various forms of cancer including smooth muscle tumors, Hodgkin’s lymphoma, and cervical cancer. A rough outline of the progression from NKD to cancer is shown below.


NKD-Associated Virus-Induced Cancer Progression

NKD → EBV/HPV → Cancer

Fewer NK cells → Easier for viruses and cancer cells to spread


It is clear from the above example that a decrease in NK cells can lead to an increased chance of infection and subsequent development of infection-induced cancer. But what impacts the number of NK cells in circulation? A study in 1996 by Irwin, McClintick, and colleagues published in the Federation of American Societies for Experimental Biology Journal details how NK cell levels change based on the amount of sleep a person gets each night. The study revealed that when participants got only 5 hours of sleep on just one given night, NK cell number and activity dropped below 50% of baseline values. (9) More recent studies have confirmed this relationship and revealed that physical activity and stress levels may also affect NK cell levels. (10) While there are many other factors that also affect NK cell values, it is important to recognize how the everyday choices we make can affect our susceptibility to viruses known to induce cancers.


Current research on virus-based cancers shows encouraging progress in a field that remains largely shrouded in mystery. We are only at the tip of the iceberg. There is so much more that we still have yet to uncover. Join us in our mission to bring awareness and fund infection-induced cancer research to put an end to virus-induced cancer once and for all!


-Ian


(1) Widmaier, E. P.; Vander, A. J.; Raff, H.; Strang, K. T.; Shoepe, T. C. Vanders human physiology: the mechanisms of body function, 15th ed.; McGraw-Hill Education: New York, NY, 2019.


(2) Grossenbacher, S. K.; Canter, R. J.; Murphy, W. J. Natural Killer Cell Immunotherapy to Target Stem-like Tumor Cells. Journal for Immunotherapy of Cancer 2017, 17 (3), 313–324. doi: 10.1080/14712598.2017.1271874.


(3) Moon, W. Y.; Powis, S. J. Does Natural Killer Cell Deficiency (NKD) Increase the Risk of Cancer? NKD May Increase the Risk of Some Virus Induced Cancer. Frontiers in Immunology 2019, 10, 1703. doi: 10.3389/fimmu.2019.01703


(4) Brown, K. F.; Rumgay, H.; Dunlop, C.; Ryan, M.; Quartly, F.; Cox, A.; Deas, A.; Elliss-Brookes, L.; Gavin, A.; Hounsome, L.; Huws, D.; Ormiston-Smith, N.; Shelton, J.; White, C.; Parkin, D. M. The Fraction of Cancer Attributable to Modifiable Risk Factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. British Journal of Cancer 2018, 118 (8), 1130–1141. doi: 10.1038/s41416-018-0029-6


(5) Biological agents. International Agency for Research on Cancer: Lyon, 2012; Vol. 100B.


(6) HPV Fast Facts. http://www.ashasexualhealth.org/stdsstis/hpv/fast-facts/


(7) HPV-Associated Cancer Statistics. https://www.cdc.gov/cancer/hpv/statistics/index.htm.


(8) Sullivan, K. E.; Stiehm, E. R. Stiehms immune deficiencies; Elsevier Acad. Press: Amsterdam, 2015. doi: 10.1016/C2012-1-01317-3.


(9) Irwin, M.; Mcclintick, J.; Costlow, C.; Fortner, M.; White, J.; Gillin, J. C. Partial Night Sleep Deprivation Reduces Natural Killer and Cellular Immune Responses in Humans. The FASEB Journal 1996, 10 (5), 643–653. doi: 10.1096/fasebj.10.5.8621064.


(10) Fondell, E.; Axelsson, J.; Franck, K.; Ploner, A.; Lekander, M.; Bälter, K.; Gaines, H. Short Natural Sleep Is Associated with Higher T Cell and Lower NK Cell Activities. Brain, Behavior, and Immunity 2011, 25 (7), 1367–1375. doi: 10.1016/j.bbi.2011.04.004.

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