A new study led by University of Oxford researchers has revealed that a common and usually harmless virus may positively influence how skin cancer patients respond to current treatments.
Cytomegalovirus (CMV) is a common virus that, while typically asymptomatic, is carried for life by 50 to 60 percent of adults in the UK. In healthy individuals, CMV is kept in a dormant state by the immune system; however, this process profoundly reshapes how the immune system operates.
The study, published in Nature Medicine, explored how CMV affected the immune responses of 341 melanoma patients receiving immunotherapy, a form of cancer treatment that helps harness the immune system to recognise and fight cancer. The research was supported by the NIHR Oxford Biomedical research Centre.
Melanoma is a cancer of the skin that can be difficult to cure if not caught early. Immunotherapies have improved the survival rates of melanoma, but not all patients benefit, and some go on to develop resistance. Occasionally, patients develop side-effects from immunotherapy (especially those receiving combination treatments), which can be life-changing and, in some cases, fatal.
This research, which is the first of its kind, suggests that CMV infection may improve treatment outcomes in melanoma patients receiving less intensive immunotherapy, while also markedly reducing the frequency of severe side-effects. The researchers also found that CMV infection potentially delays melanoma from developing and spreading, indicating that the immune response to CMV might also impact cancer development.
Among the key findings were:
Better Immunotherapy Response
CMV-positive patients were found to have a better response to single-drug PD-1 therapy, which works by blocking the PD-1 protein to help the immune system attack cancer cells. Among patients receiving this therapy to prevent melanoma relapse, those with CMV were also less likely to experience recurrence. However, response rates were found to be unchanged with combination therapies. This suggests that testing CMV status may help doctors to better personalise immunotherapy for melanoma in the future.
Fewer Serious Side-Effects
CMV-positive patients experienced lower rates of severe immune-related complications during treatment, most notably colitis (inflammation of the colon). This suggests that knowledge of a patient’s CMV status before treatment could help anticipate, prevent or better manage side-effects.
Possible Protection Against Metastatic Melanoma (MM)
People with CMV were found to develop metastatic melanoma (cancer that has spread from the skin to other parts of the body) later in life compared to those without CMV. Patients with BRAF-mutated tumours (a change in the BRAF gene that can cause uncontrolled cell growth and is present in around 40 percent of melanoma patients) appeared to receive additional protection. This finding suggests that the virus may offer some protection against MM. Further research into how CMV achieves this could support the development of therapies aimed at preventing melanoma recurrence.
The research team, led by Professor Benjamin Fairfax, Professor of Cancer Immunogenetics at the University of Oxford, found that these effects are likely due to the CMV virus stimulating a group of T cells, immune cells that are crucial in the fight against cancer.
Commenting on the findings, Professor Fairfax said: “Current immunotherapies for cancer can cause serious side-effects in some patients, which may occasionally lead to lifelong complications. Prior CMV infection in a patient could help determine, on a patient-by-patient basis, whether immunotherapies are likely to be effective or cause side-effects, serving as a key factor in deciding which treatments to give.
Our work also has potentially fundamental implications for our understanding of skin cancer development, because it shows that factors which influence the immune system independently of cancer can have unanticipated effects on melanoma development.”
This is the first time a common virus, unrelated to cancer, has been shown to influence both melanoma development and treatment response. Further research is needed to confirm these findings in larger patient populations and to explore whether CMV-based strategies could be leveraged to enhance the effectiveness of current immunotherapies.
However, these discoveries could open new avenues for personalised immunotherapy approaches, enabling better targeting of drugs to those most in need, and reducing the risk of harmful side-effects. The findings also suggest that a patient’s viral infection history may be a key factor in predicting treatment success.
As well as the NIHR Oxford BRC, this research was funded by Wellcome, with input from Cancer Research UK and the CRIS Cancer Foundation.