Common Virus Improves Melanoma Treatment Response, Reduces Side Effects

A common virus carried by approximately half of adults worldwide may improve outcomes for melanoma patients receiving immunotherapy while also protecting against severe treatment-related side effects and limiting the spread, according to new research from the University of Oxford.

The study, published in Nature Medicine, found that patients with cytomegalovirus (CMV) who received single-agent anti-PD-1 immunotherapy for metastatic melanoma had significantly improved survival compared with CMV-negative patients. Benjamin P. Fairfax, Ph.D., professor of Cancer Immunogenetics at the University of Oxford, led the study.

Benjamin P. Fairfax, Ph.D.

“Our work also has potentially fundamental implications for our understanding of skin cancer development, because it shows that factors that influence the immune system independently of cancer can have unanticipated effects on melanoma development,” said Fairfax in a news release.

CMV is a herpes virus and is related to the viruses that cause chickenpox, herpes simplex and mononucleosis. It usually goes dormant after infection, but it can permanently “re-wire” T cells, the white-blood-cell assassins that checkpoint drugs unleash on tumors.

In the 340 melanoma patients analyzed by researchers, those who were CMV-positive had more immune cells circulating in their blood before they started immunotherapy. This higher baseline may be one reason why these patients responded better to certain immunotherapy treatments, the study said.

Immune cells from CMV-positive patients had higher expression of genes associated with cytotoxicity and inflammation, which are important for fighting cancer. The researchers identified a specific gene that helps coordinate immune cell activity that appears to be the main driver of this effect.

One of the most surprising findings was that CMV-positive patients experienced approximately 40% fewer severe side effects from immunotherapy than those without the virus. This was particularly notable for side effects like colitis and pneumonitis, which can be life-threatening complications of immunotherapy. The data suggest that CMV infection somehow makes the immune system more selective in its targets, reducing off-target effects while maintaining cancer-fighting ability.

“Current immunotherapies for cancer can cause serious side-effects in some patients, which may occasionally lead to lifelong complications,” Fairfax said in the release. “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.”

The researchers found that while single-agent immunotherapy worked better in CMV-positive patients, combination therapy showed similar effectiveness regardless of CMV status. This suggests that more aggressive combination therapy may compensate for the immune differences seen in CMV-negative patients.

The study also uncovered an unexpected connection between CMV and melanoma development. The researchers found that metastatic melanoma patients were less likely to be CMV-positive compared with the general population, potentially offering some protection against the cancer.

Additionally, CMV-positive patients with one of the main genetic subtypes of melanoma (linked to BRAF mutations) did not develop metastatic disease until nearly a decade later than CMV-negative patients, suggesting the virus may delay some forms of the cancer from progressing to advanced stages.

According to the American Cancer Society, more than 100,000 new melanomas will be diagnosed in the United States this year, and more than 8,400 people are expected to die from the condition. While the average age of diagnosis is 66, the cancer is one of the most prevalent among those younger than 30. When caught early, nearly every patient survives, but the 5-year survival rate drops to 35% when melanoma metastasizes.