A common virus carried by more than half of UK adults may significantly improve outcomes for melanoma patients receiving immunotherapy, according to groundbreaking research led by the University of Oxford.
The study, published in Nature Medicine, examined 341 melanoma patients and found that those previously infected with cytomegalovirus (CMV) showed better responses to certain immunotherapy treatments and experienced fewer severe side effects.
CMV Infection Linked to Improved Treatment Response
Cytomegalovirus, a typically asymptomatic virus carried by approximately 50-60% of UK adults, appears to create favorable conditions for immunotherapy effectiveness. While the virus remains dormant in healthy individuals, the immune system's ongoing suppression of CMV significantly alters immune function in ways that may benefit cancer patients.
The Oxford team discovered that CMV-positive melanoma patients responded better to single-drug PD-1 inhibitor therapy, which helps the immune system recognize and attack cancer cells. Among patients receiving this therapy to prevent melanoma recurrence, those with CMV were less likely to experience disease relapse.
"Current immunotherapies for cancer can cause serious side-effects in some patients, which may occasionally lead to lifelong complications," explained Professor Benjamin Fairfax, professor of cancer immunogenetics at the University of Oxford and lead researcher. "Prior cytomegalovirus 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."
Interestingly, the researchers found no difference in response rates among patients receiving combination immunotherapy regimens, suggesting that CMV status could be particularly valuable for personalizing single-agent treatment approaches.
Reduced Side Effects in CMV-Positive Patients
One of the most significant findings was that patients with CMV experienced lower rates of severe immune-related complications during treatment. Most notably, these patients had reduced incidence of colitis, a potentially serious inflammation of the colon that can be triggered by immunotherapy.
This discovery suggests that testing for CMV status before beginning treatment could help clinicians better anticipate, prevent, or manage treatment-related side effects, potentially improving patient quality of life during therapy.
Potential Protective Effect Against Cancer Progression
Beyond treatment response, the study revealed that CMV infection may actually delay the development and spread of melanoma. Researchers observed that CMV-positive individuals developed metastatic melanoma—cancer that has spread from the skin to other parts of the body—later in life compared to those without the virus.
Patients with tumors harboring BRAF mutations (occurring in approximately 40% of melanoma cases) appeared to receive additional protection, suggesting the virus may provide some defense against melanoma progression.
The research team concluded that these effects likely stem from CMV's stimulation of specific T cells, immune cells crucial in fighting cancer. This stimulation appears to create an immune environment that both enhances treatment efficacy and potentially slows cancer development.
Implications for Personalized Medicine
This study represents the first time a common virus unrelated to cancer has been shown to influence both melanoma development and treatment response. The findings could have profound implications for personalizing immunotherapy approaches.
Testing for CMV status could become a valuable biomarker to help oncologists determine which patients might benefit most from single-agent PD-1 inhibitor therapy versus more aggressive combination approaches. This could allow for more tailored treatment decisions, potentially sparing some patients from unnecessary side effects while ensuring others receive appropriately intensive therapy.
While further research is needed to confirm these findings in larger patient populations and explore whether CMV-based strategies could enhance existing immunotherapies, this discovery opens new avenues for understanding how a patient's viral history may influence cancer treatment outcomes.
The study also highlights how factors affecting the immune system independently of cancer may have unexpected effects on both cancer development and treatment response, potentially leading to new therapeutic strategies in the future.
