PEOPLE WITH NON-SMALL CELL LUNG CANCER (NSCLC) or metastatic melanoma who received a messenger RNA (mRNA)-based COVID-19 vaccine around the time they started immunotherapy lived significantly longer than patients who did not receive a vaccine, according to a new study. The findings provide more information about how mRNA-based vaccines may enhance the immune system’s ability to protect against not just the coronavirus but also cancer.

The study, published Oct. 22, 2025, in Nature, compared the survival of people who had received an mRNA-based COVID-19 vaccine within 100 days of starting immunotherapy and people who had not been vaccinated. The study examined records from 884 people with stage III or IV NSCLC and 210 people with metastatic melanoma who received treatment with an immune checkpoint inhibitor. Immune checkpoint inhibitors work by blocking proteins that prevent the immune system from attacking healthy cells but also allow cancer cells to evade detection. COVID-19 vaccines that use mRNA can instruct human cells to create the spike protein associated with the coronavirus, which trains the immune system to recognize this key feature and prevent or lessen the effects of future infections.

Researchers found that people with NSCLC who received an mRNA-based COVID-19 vaccine lived significantly longer than those who didn’t receive the vaccine. The three-year overall survival, the percentage of patients alive three years after starting immune checkpoint inhibition, was 55.7% in the mRNA-based COVID-19 vaccine group versus 30.8% in those who had not been vaccinated. Results were similar for people with metastatic melanoma. Three-year overall survival was 67.6% for those in the mRNA-based COVID-19 vaccine group versus 44.1% for those who had not received the vaccine.

Building on this finding, the study’s researchers turned to mouse models to explore how mRNA-based vaccines might prompt immune responses that attack and destroy tumors. “We found that the COVID-19 mRNA vaccine acts like a siren to activate all of the immune cells throughout your body,” says Adam Grippin, the study’s lead author and a cancer immunotherapy researcher at the University of Texas MD Anderson Cancer Center in Houston. “When this happens in a patient with cancer, those immune cells inside the tumor start programming other immune cells to kill cancer. The effects are powerful.”

In their mouse models, Grippin and his team found that mRNA-based COVID-19 vaccines trigger a massive increase in interferon alpha, a molecule that stimulates immune cells, enhancing the body’s ability to fight off infections and other diseases. Researchers tested blood samples from healthy volunteers after receiving a COVID-19 vaccine and found higher levels of interferon alpha and signs of increased activity from the immune system’s T cells and natural killer cells. The researchers say that ICI treatment may expand these effects allowing greater immune activity against cancer. “We found that mRNA vaccines, combined with immune checkpoint blockade, can fan a powerful flame that can overwhelm the tumor,” Grippin says.

Many cancer researchers have been focused on developing personalized mRNA-based cancer vaccines. Labs build these vaccines around features from a person’s cancer cells to help mobilize the immune system to attack cancer and prevent recurrence. “This study gives us pause because it doesn’t fit that concept,” says Patrick Ott, a medical oncologist and director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute in Boston, who was not involved in the study. “It supports the premise that mRNA COVID vaccines can have an off-target effect, by providing additional stimulation to help immune checkpoint inhibitors be more effective against cancer,” Ott says.

Grippin and his team are planning a randomized phase III clinical trial to compare the outcomes of patients receiving immunotherapy plus an mRNA-based COVID-19 vaccine with patients receiving immunotherapy alone.

Recently, “mRNA vaccines have become a flashpoint in society,” Grippin says. Health and Human Services Secretary Robert F. Kennedy Jr. and others have claimed mRNA vaccines do not “perform well” against upper lung infections and that they are dangerous, but scientists maintain that mRNA vaccines prevented deaths from COVID-19 and show promise against other diseases. “Our hope is that data from our randomized clinical trial will show a benefit of these therapies and maybe change the conversation around these drugs,” Grippin says. Two mRNA-based COVID-19 vaccine options, from Moderna and Pfizer-BioNTech, are available in the U.S.

Sandra Gordon is a medical writer in Stamford, Connecticut.