Widespread virus may improve skin cancer treatment outcomes

A new study led by scientists at Oxford University has found that a common and usually harmless virus can positively influence the response of skin cancer patients to existing treatments.

Cytomegalovirus (CMV) is a common virus that is usually asymptomatic, but around 50-60% of UK adults carry it. In healthy individuals, CMV is kept dormant by the immune system. However, the process fundamentally alters the way the immune system works. A study published in Nature Medicine examined how CMV affects the immune responses of 341 melanoma patients receiving immunotherapy, a type of cancer treatment that helps engage the immune system to recognize and fight malignancies.

Melanoma is a skin cancer that is difficult to cure if not detected early. Immunotherapy has improved survival rates for melanoma, but it does not help all patients, and some develop resistance later in life. Sometimes patients develop side effects of immunotherapy (especially in those receiving combination treatment) that can change the life they are used to and, in some cases, can be fatal.

This study, which is the first of its kind, suggests that CMV infection may improve outcomes for melanoma patients receiving less intensive immunotherapy, as well as markedly reduce the incidence of severe side effects. The researchers also found that CMV infection potentially delays the development and spread of melanoma, suggesting that the immune response to CMV may also influence cancer development.

Key findings from the study include:

• Better response to immunotherapy: CMV-positive patients responded better to therapy with a single drug that blocks the PD-1 protein, which helps the immune system attack cancer cells. Among patients receiving this therapy to prevent melanoma recurrence, CMV patients were also less likely to experience relapses. However, response rates did not change with the combination treatment. This suggests that checking CMV infection status may help physicians better personalize melanoma immunotherapy in the future.
• Fewer serious side effects: CMV-positive patients experienced fewer serious immune-related complications during treatment, most notably colitis (inflammation of the colon). This suggests that knowing a patient’s CMV status prior to treatment may help predict, prevent, or better manage side effects.
• Possible protection against metastatic melanoma (MM): people with CMV have been found to develop metastatic melanoma (cancer that has spread from the skin to other parts of the body) later compared to those without CMV. Patients with tumors with a BRAF mutation (a change in the BRAF gene that can cause uncontrolled cell growth and occurs in about 40% of melanoma patients) appeared to receive additional protection. This finding suggests that the virus may provide some protection against MM. Further study of how CMV provides this protection may help in the development of therapies aimed at preventing melanoma recurrence.

A research team led by Professor Benjamin Fairfax, Professor of Cancer Immunogenetics at the University of Oxford, concluded that these effects are likely due to the fact that the CMV virus stimulates a group of T cells, immune cells that are crucial in the fight against cancer.

Commenting on the findings, Professor Fairfax said: “Current cancer immunotherapies can cause serious side effects in some patients, which can sometimes lead to lifelong complications. Previous CMV infection in a patient can help determine whether immunotherapy will be effective or cause side effects, and serve as a key factor in deciding which treatment to administer.”

The scientists’ work also has potentially fundamental implications for understanding the development of skin cancer, as it shows that factors that affect the immune system independently of the presence of cancer may have unanticipated effects on melanoma development.

For the first time, a common virus unrelated to cancer has been shown to influence both melanoma development and response to treatment. Further studies are needed to confirm these findings in larger patient populations and to see if CMV-based strategies can be used to enhance the efficacy of existing immunotherapies.

However, these findings may open new avenues for personalized approaches to immunotherapy, allowing drugs to be better tailored to the patients who need them most and reducing the risk of harmful side effects. The findings also suggest that a patient’s history of viral infections may be a key factor in predicting treatment success.