Cancer patients with advanced lung and skin cancers who received COVID-19 mRNA vaccines during immunotherapy treatment lived substantially longer than those who didn’t, according to groundbreaking research presented at the 2025 European Society for Medical Oncology Congress in Berlin and published in the journal Nature.
The study, led by researchers at the University of Texas MD Anderson Cancer Center and the University of Florida, analyzed medical records from more than 1,000 patients with stage 3 or 4 non-small cell lung cancer and metastatic melanoma treated between August 2019 and August 2023. The findings have prompted scientists to design a randomized Phase 3 clinical trial to determine whether COVID mRNA vaccines should become standard care alongside cancer immunotherapy.
The research revealed striking differences in survival times between vaccinated and unvaccinated patients receiving immune checkpoint inhibitors, a type of immunotherapy that helps the immune system recognize and attack cancer cells.
Among patients with advanced non-small cell lung cancer, those who received an mRNA COVID vaccine within 100 days of starting immunotherapy had a median survival of 37.3 months, compared to 20.6 months for unvaccinated patients—representing a near doubling of survival time. The three-year overall survival rate jumped from 30.6% to 55.8% with vaccination.
For metastatic melanoma patients, the results were even more remarkable. Median survival increased from 26.7 months among unvaccinated patients to between 30 and 40 months for vaccinated patients. At the time data collection ended, some vaccinated patients were still alive, meaning the actual survival benefit could be even greater.
The cancer-fighting effect has nothing to do with COVID-19 protection. Instead, the mRNA technology itself appears to activate the immune system in ways that enhance the body’s ability to recognize and destroy tumor cells.
The research team discovered that mRNA vaccines work by stimulating a surge in inflammatory cytokines—signaling proteins that alert the immune system. When patients received an mRNA vaccine, it functioned as an alarm that triggered immune cells to move from the tumor microenvironment to lymph nodes, where they could be properly activated to attack cancer cells.
At the molecular level, the vaccines activate innate immune signaling pathways and prime adaptive T cell responses, thereby enhancing the immune environment at tumor sites. The immune activation triggered by mRNA vaccines also induces upregulation of PD-L1 on tumor cells, which paradoxically makes them more susceptible to immune checkpoint inhibitors that block the PD-1/PD-L1 pathway.
To validate their clinical observations, the University of Florida research team conducted experiments using mouse models. When mice received a combination of immunotherapy drugs and an mRNA vaccine targeting the COVID-19 spike protein, tumors that had previously been unresponsive to treatment began to shrink.
These preclinical studies confirmed similar mechanisms observed in human patients, including immune activation in healthy volunteers and increased PD-L1 expression on tumors in vaccinated cancer patients. Importantly, the survival improvements persisted regardless of vaccine manufacturer, number of doses, or when patients received treatment at MD Anderson.
Patients who received non-mRNA vaccines, such as pneumonia or flu shots, did not experience the same survival benefits, suggesting the effect is specific to mRNA-based vaccines.
The current findings from the analysis of more than 1,000 patient records are preliminary and observational in nature. As with any retrospective study, the results require confirmation from a prospective, randomized clinical trial.
A multi-center, randomized Phase 3 clinical trial is currently being designed to validate these findings and investigate whether COVID mRNA vaccines should be part of the standard of care for patients receiving immune checkpoint inhibition.
