Cancer vs Natural Killer Cells – The Battle Continues…

Cancer is on the march. The World Health Organisation (WHO) estimates that by 2020 the number of individuals affected by cancer could increase by 50% to 15 million. Ageing populations and increasingly unhealthy lifestyles are the main reasons for this shocking prediction. However, scientists are fighting back and today more people than ever are surviving a cancer diagnosis.

Nevertheless, many obstacles must be tackled in order to combat cancer completely. For example, a recent study, conducted by researchers from the University of Tokyo, has shown that specific cancer cells have evolved to overcome natural killer (NK) cell defence.

Natural killer cell defence

NK cells are an important part of the immune system; they are capable of recognising and destroying virus-infected and tumorous cells. They can distinguish between normal and abnormal cells because they are attracted to an ‘activating signalling protein’, which is produced in greater quantities by cancerous cells compared to normal cells. Once this ‘signalling protein’ binds to its receptor site, it stimulates the NK cell to release toxins that will ultimately destroy the tumour.

Cancerous cells compromise body’s ability to destroy tumour with toxins

However, the researchers discovered that cancer-associated fibroblasts, or CAFs, have evolved a mechanism to render NK cells ineffective. CAFs are an important component of the tumour micro-environment, promoting tumour growth and encouraging inflammation. Interestingly, these cancerous cells produce the ‘signalling protein’ in much lower quantities (compared to normal cells), therefore the NK cells are not activated. Consequently, the tumour can then remain undetected and pose an ongoing threat.

These results were confirmed using ‘RNA interference’, which allowed the team to manipulate normal cells to produce less ‘signalling protein’, thus resembling the CAFs identified in the study.  As anticipated, these ‘normal’ cells also suppressed NK cell activity, confirming that a reduction in ‘signalling protein’ is the essential factor in this process.

Further investigation is needed to improve our understanding of specifically how a reduction in ‘signalling protein’ suppresses NK cell activity, thus impairing the effectiveness of NK-cell based therapies. Only then can we develop new treatments – taking us one step closer to defeating cancer once and for all.

Reference: Inoue, T., Adachi, K., Kawana, K., Taguchi, A., Nagamatsu, T., Fujimoto, A., Tomio, K., Yamashita, A., Eguchi, S., Nishida, H. and Nakamura, H., 2016. Cancer-associated fibroblast suppresses killing activity of natural killer cells through downregulation of poliovirus receptor (PVR/CD155), a ligand of activating NK receptor. International Journal of Oncology.

Author: Kate Porter

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