Radiotherapy - does it really do more harm than good?

“Could radiotherapy do more harm than good in some patients?” the Daily Mail asks. 

The question is prompted by a new study looking at whether radiotherapy could lead to a type of cell, known as Langerhans cells, reducing the immune system’s ability to fight cancers, such as skin cancer.

They identified a protein which enabled these Langerhans cells to rapidly repair DNA damage caused by radiotherapy, and therefore survive. When mice were exposed to radiation, these cells also caused a suppression of their immune response to skin tumours, and greater tumour growth.

While the Mail’s headline might cause alarm to cancer patients and their families, it is important to remember that radiotherapy is a vital, and sometimes life-saving, aspect of many people’s treatments.

It should also be noted that this study was carried out on mice, and the radiation was given to the mice’s whole bodies shortly before they were injected with skin cancer cells. In humans, radiotherapy is directed specifically at an existing cancer site – therefore, the impact of these cells may not be exactly the same.

Researchers will now investigate further to see if these cells really contribute to radiation resistance in human cancer, and whether they can use this knowledge to improve the response of cancers to radiotherapy.

Where did the story come from?

The study was carried out by researchers from Icahn School of Medicine at Mount Sinai, New York. Funding was provided by the US National Institutes of Health, the American Medical Association, the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the US National Institutes of Health, and the National Cancer Institute of the US National Institutes of Health. There were no conflicts of interest reported.

The study was published in the peer-reviewed medical journal Nature Immunology.

The headline in the Mail is bound to cause alarm, but readers should note the warning from an independent expert to “not throw the baby out with the bath water”, explaining that radiotherapy has an important part to play in the treatment of skin cancer.

What kind of research was this?

This was an animal study on mice assessing the effect of ionising irradiation (radiotherapy) on one type of immune system cells, called Langerhans cells. These are present in the outer layers of the skin and are known to be resistant to radiation.

Radiotherapy acts by damaging the DNA of cancer cells, killing them. While some research has suggested that radiotherapy may also help the immune system to attack cancers, other studies have suggested that it may also dampen some aspects of the immune response.

 The researchers wanted to assess whether Langerhans cells might be contributing to this dampening, as it might then lead to cancer cells sometimes becoming resistant to radiotherapy. By understanding how radiotherapy resistance comes about, they hope to find ways to combat it and make radiotherapy more effective.

While the findings of animal studies may not be completely representative of what will be seen in humans, they do provide a starting point for further research.

What did the research involve?

The researchers exposed mice to radiotherapy to assess the resistance of Langerhans cells to apoptosis (cell death) after therapy. They then investigated whether the Langerhans cells were able to repair their DNA damage caused by the radiation, and which proteins in the cells might be helping them do this.

They then looked at what happened if they gave mice a whole-body dose of radiation, and then injected them with skin cancer cells. They compared this with what happened in mice not radiated before injecting them with skin cancer cells.

What were the basic results?

The study found that Langerhans cells did not undergo cell death after exposure to radiotherapy like normal cells; instead they managed to rapidly repair the radiation damage to their DNA. Langerhans cells were found to produce increased levels of proteins that could help them to survive, particularly one protein called cyclin-dependant kinase inhibitor (CDKN1A). Langerhans cells in mice genetically engineered to lack this protein were less resistant to radiation and not as able to repair radiation-induced DNA damage.

The researchers found that after radiation, Langerhans cells migrated to the lymph nodes and caused an increase in the number of another type of immune system cell, called Treg cells. These cells get into tumours and can reduce the immune system’s ability to fight the tumour.

Finally, the researchers showed that if they gave mice a whole-body dose of radiation and then injected them with skin cancer cells the next day, they grew larger tumours than non-irradiated mice. 

The irradiated mice had more Treg cells in their tumours, and more Langerhans cells in their lymph nodes. This effect was short-lived, as mice injected with skin cancer cells five weeks after irradiation did not grow larger tumours.

How did the researchers interpret the results?

The researchers say they “found that [Langerhans cell] resisted apoptosis and rapidly repaired DNA damage after exposure to [ionising radiation]” and that the protein CDKN1A appears to help the cells do this. They say their findings might help them to develop a way of enhancing the response of cancers to radiotherapy.

Conclusion

This was an animal study looking at the effect of radiotherapy on a particular type of immune system cell found in the skin, called Langerhans cells. The high-energy radiation used in radiotherapy normally permanently damages the DNA of cancer cells, causing them to die. However, Langerhans seem able to repair this damage and survive.

The study found that a protein, CDKN1A, allows Langerhans cells to resist cell death and repair damage to DNA after exposure to radiotherapy. The cells also seemed capable of suppressing mice’s immune response to the tumours. 

This study was on mice, so we cannot be sure the same effect would be seen in humans, particularly as these mice were given whole-body radiation before being injected with cancer cells. In human cancer, radiotherapy is directed specifically at an existing cancer.

The identification of this protein is of interest, as it may provide a route for further research to see if the effectiveness of radiotherapy can be improved for some patients. More laboratory and animal research will be needed before we know if this will become a reality.

The aim of radiotherapy is to give the highest chance of curing or shrinking the cancer, while reducing the risk of side effects. For many people it is an integral and effective part of their cancer treatment.

This study should not be seen as a warning against radiotherapy, but rather a possible means for further improving its outcomes in the future.  

Links To The Headlines

Could radiotherapy do more harm than good in some patients? Treatment may ‘suppress the body’s natural ability to fight skin cancer’. Daily Mail, September 8 2015

Links To Science

Price JG, Idoyaga J, Salmon H, et al. CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation. Nature Immunology. Published online September 7 2015