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 starting treatment, according to a new study led by researchers at The University of Texas MD Anderson Cancer Center.
These findings, which include more than 1,000 patients treated between August 2019 and August 2023, were presented today at the European Society of Medical Oncology (ESMO) 2025 Congress (Abstract LBA54). The study was led by Steven Lin, MD, Ph.D. professor of Radiation Oncology and Adam Grippin, MD, Ph.D., senior fellow in Radiation Oncology.
This study demonstrates that commercially available vaccines for COVID-19 can train patients’ immune systems to eradicate cancer. When combined with immune checkpoint inhibitors, these vaccines produce strong antitumor immune responses associated with vast improvements in survival for cancer patients.”
Adam Grippin, MD, Ph.D., senior fellow in Radiation Oncology
How was this correlation discovered?
The discovery that mRNA vaccines were potent immune activators came from research conducted by Grippin during his graduate work at the University of Florida in the lab of Elias Sayour, MD, Ph.D. In developing personalized mRNA-based cancer vaccines for brain tumors, Grippin and Sayour discovered that the mRNA vaccines trained the immune system to eliminate cancer cells, even when the mRNA did not directly target the tumors.
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 began 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.
How do anti-mRNA vaccines impact cancer immunotherapies?
To better understand the mechanisms that may help explain the clinical data, the Lin and Sayour labs at both institutions studied preclinical models. They discovered that mRNA vaccines act like an alarm, putting the body’s immune system on high alert to recognize and attack cancer cells.
In response, the cancer cells begin to produce the immune checkpoint protein PD-L1, which acts as a defense mechanism against the immune cells. Fortunately, several immune checkpoint inhibitors have been designed to block PD-L1, creating a perfect environment for these therapies to unleash the immune system against cancer.
These preclinical observations were also confirmed in clinical studies. The researchers found similar mechanisms, including immune activation in healthy volunteers and increased PD-L1 expression in tumors in patients who received mRNA vaccines for COVID.
Although the mechanisms are not yet fully understood, this study suggests that COVID mRNA vaccines are powerful tools for reprogramming immune responses against cancer.
What are the main implications of this discovery?
“The really exciting part of our work is that it points to the possibility that widely available, low-cost vaccines have the potential to dramatically improve the effectiveness of some immune therapies,” Grippin said. “We are optimistic that mRNA vaccines could not only improve outcomes for patients treated with immunotherapies, but also bring the benefits of these therapies to patients with treatment-resistant disease.”
A multicenter, randomized Phase III trial is currently being planned to validate these findings and investigate whether COVID mRNA vaccines should be part of the standard of care for patients receiving immune checkpoint inhibition.
What are the key data from this study about COVID mRNA vaccines and immunotherapy outcomes?
This study included multiple groups of various cancer types, evaluating patients who had received an mRNA vaccine within 100 days of starting immunotherapy treatment.
In the first group, 180 patients with advanced non-small cell lung cancer who received the vaccine had a median survival of 37.33 months, compared with 20.6 months in 704 patients who did not receive the vaccine. In a group of patients with metastatic melanoma, median survival was 26.67 months in 167 patients who did not receive the vaccine, but it had not yet been reached in 43 patients who received the vaccine – indicating a significant improvement.
Importantly, these survival improvements were most pronounced in patients with immunologically “cold” tumors, which are not expected to respond well to immunotherapy. These patients, who have very low PD-L1 expression in their tumors, experienced a nearly fivefold improvement in three-year overall survival by receiving a COVID vaccine.
The findings were consistent even when independent factors such as vaccine manufacturer, number of doses and when patients were treated at MD Anderson were taken into account.
