Ancient viral DNA in our genomes help fight lung cancer

Our immune system can use antibodies recognising fragments of ancient viruses to help fight lung cancer, according to a study by researchers in London.

Scientists at University College London and the Francis Crick Institute, London, wanted to help understand why some lung cancer patients do better than others when receiving checkpoint inhibitors as an intravenous drug treatment, which is an immunotherapy that activates immune cells to help them overcome the hurdles that cancer cells build to protect themselves. In particular, they wanted to look at why patients with more B cells – responsible for producing antibodies – close to their tumours tend to do better on checkpoint inhibitors drug treatment.

'There is a huge focus on the activity of T cells against cancer because of their ability to destroy tumour cells. But our work highlights an important role for antibody responses and also how these responses might be boosted with immunotherapy', said joint first-author Dr Katey Enfield from the Francis Crick Institute. 'Our study also helps to explain the mechanism by which the presence of B cells in tumours improves patient response to immunotherapy.'

Publishing their results in Nature, lung cancer cells were shown to often produce proteins from 'endogenous retroviruses' ('ERVs'), which infected our ancestors as we evolved and became incorporated into our genomes. Looking at both lung cancer patient samples and mouse models, they saw that these proteins became the target of antibodies. These antibodies can then act as a flag, helping other immune cells kill or suppress cancer cells.

Furthermore, the amount of ERV expressed in the cancer cells correlated with more ERV-targeting antibodies, which increased after treatment with checkpoint inhibitors. Similarly, when the scientists prevented the mouse models from making the antibodies, they showed that the mice did not respond well to treatment with checkpoint inhibitors, helping explain why having antibody-producing B cells close by could help.

Hence, while usually dormant, these ancient viral fragments can become expressed in cancerous cells providing a target for the immune system, which may provide researchers with new therapeutic options.

The scientists involved in this study hope to exploit their findings in future translational work. 'With more research, we could look to develop a cancer treatment vaccine made up of activated ERV genes to boost antibody production at the site of a patient's cancer and hopefully improve the outcome of immunotherapy treatment.', said Professor George Kassiotis, head of the Retroviral Immunology Laboratory at the Francis Crick Institute and one of the lead authors.