Cancer patients who received mRNA-based COVID vaccines within 100 days of starting immune checkpoint therapy were twice as likely to be alive three years after beginning treatment, according to a new study led by researchers at The University of Texas MD Anderson Cancer Centre.
These findings, which include more than 1,000 patients treated between Aug. 2019 and Aug. 2023, were presented today at the 2025 European Society for Medical Oncology (ESMO) Congress (Abstract LBA54). The study was led by Steven Lin, M.D., PhD, professor of Radiation Oncology, and Adam Grippin, M.D., PhD, senior resident in Radiation Oncology.
The discovery that mRNA vaccines were powerful immune activators came from research conducted by Grippin during his graduate work at the University of Florida in the lab of Elias Sayour, M.D., PhD. While developing personalised mRNA-based cancer vaccines for brain tumours, Grippin and Sayour found that mRNA vaccines trained immune systems to eliminate cancer cells, even when the mRNA didn’t target tumours directly.
This finding led to the hypothesis that other types of mRNA vaccines might have the same effect, and the approval and use of mRNA-based COVID vaccines created an opportunity to test this hypothesis. Lin and Grippin initiated a major effort to retrospectively study whether MD Anderson patients who received mRNA COVID vaccines lived longer than those who did not receive these vaccines.
To better understand the mechanisms at work that can help explain the clinical data, the Lin and Sayour labs at both institutions studied preclinical models. They discovered that mRNA vaccines work like an alarm, putting the body’s immune system on high alert to recognise and attack cancer cells.
In response, the cancer cells start making the immune checkpoint protein PD-L1, which works as a defence mechanism against immune cells. Fortunately, several immune checkpoint inhibitors are designed to block PD-L1, creating a perfect environment for these treatments to unleash the immune system against cancer.
These preclinical observations held up in clinical studies as well. The investigators found similar mechanisms, including immune activation in healthy volunteers and increased PD-L1 expression on tumours in patients who received COVID mRNA vaccines.
While the mechanisms are not yet fully understood, this study suggests COVID mRNA vaccines are powerful tools to reprogram immune responses against cancer. A multi-centre, randomised Phase III 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. This study included multiple cohorts of several cancer types, evaluating patients who had received an mRNA vaccine within 100 days of starting immunotherapy treatment.
