COVID-19 vaccines could help tumors respond better to immune checkpoint inhibitors

It was found that mRNA vaccines, including the COVID-19 vaccine, can activate the immune system in a way that makes hard-to-treat tumors respond better to immunotherapy, according to a study published in Nature in October.

mRNA, short for messenger RNA, is a temporary set of instructions that tells cells how to make specific proteins, according to the American Cancer Society (ACS). Known for preventing COVID-19, mRNA vaccines teach the immune system to recognize and attack specific viral proteins.

Researchers, including those of the Nature study, are now exploring how mRNA vaccines could help the immune system spot and attack cancer cells. The ACS shared that mRNA vaccines can be made quickly and may be personalized to target a patient’s unique tumor proteins or designed to help many patients, unlike traditional cancer vaccines.

Early studies also suggest these vaccines can boost other treatments such as immune checkpoint inhibitors (ICIs). The safety of mRNA vaccines is supported by millions of those who have received COVID-19 mRNA vaccines worldwide, according to the ACS.

ICIs are drugs that block proteins such as PD-1 or PD-L1, which tumors use to hide from the immune system. Blocking these proteins can extend survival in some patients, but many tumors, including “cold” tumors, remain resistant because they lack pre-existing immune activity, according to lead author Adam J. Grippin, M.D., Ph.D., a radiation oncology resident at The University of Texas MD Anderson Cancer Center, and his team of researchers.

In the past, scientists worked on personalized mRNA cancer vaccines to help the immune system combat resistant tumors, but making these vaccines can be consuming of time and effort. Data from this study shows that commonly available mRNA vaccines, such as those for COVID-19 that target the SARS-CoV-2 spike protein, can also prep the immune system to respond better to ICIs.

According to the study, these vaccines send antiviral signals that wake up immune cells, letting more of them reach tumors, increase PD-L1 levels and make immunotherapy work better.

A large group of researchers, alongside Grippin, conducted the study to explore this area where many patients lack pre-existing anti-cancer immunity. The team wanted to see if these vaccines could stimulate the immune system to improve responses to ICIs and potentially overcome resistance.

To evaluate the relationship between mRNA vaccines and cancer immunotherapy, researchers combined retrospective patient data, experiments in healthy volunteers and preclinical mouse studies. Medical records were reviewed from MD Anderson Cancer Center for patients with advanced non-small cell lung cancer (NSCLC), melanoma or other cancers who received ICIs and their vaccination status was noted.

Survival outcomes were compared between patients who received COVID-19 mRNA vaccines within 100 days of ICI treatment and those who did not, using Kaplan–Meier analysis, Cox regression and propensity score matching.

In healthy participants, blood samples were collected at different time points after vaccination to measure immune responses, including cytokine levels and T cell activation using flow cytometry. In mice, tumor models were treated with mRNA vaccines alone or with ICIs. Tumor growth, immune cell activity and antibody responses were measured using flow cytometry, ELISA and immunofluorescence.

All animal and human studies were approved by the respective institutional review boards.

In patients with NSCLC and metastatic melanoma, researchers found that vaccination was associated with improved survival and immune responses. For NSCLC patients at MD Anderson, median overall survival (OS) was 37.3 months for vaccinated patients compared to 20.6 months for unvaccinated.

Three-year OS was 55.7% compared to 30.8%, with an adjusted hazard ratio of 0.51 (95% CI 0.37–0.71, P < 0.0001). Stage III and IV patients also showed significant survival benefits (HR 0.37 and 0.52). In metastatic melanoma, vaccinated patients had a 36-month OS of 67.6% versus 44.1% and median progression-free survival improved from 4.0 to 10.3 months (HR 0.37, 95% CI 0.18–0.74, P = 0.0048).

Data also revealed that vaccinated patients had higher levels of PD-L1 in their tumors with an average tumor proportion score (TPS) of 31% compared with 22% to 25% in those who were not vaccinated. They were also more likely to reach the 50% TPS mark.

In healthy participants, the vaccine caused a large jump in immune activity, including about a 280-fold increase in the IFNα protein and higher numbers of activated T cells and NK cells. These immune changes peaked around 24 hours after the shot and returned to normal by day 7.

These findings suggest that mRNA vaccines could offer a simple, low-cost and readily available option compared with personalized cancer vaccines.

This study, overall, holds a number of strengths because it shows that widely available COVID-19 mRNA vaccines can help ICIs work better in cancer patients even though the vaccines do not target tumor cells directly. Additionally, researchers identified how this happens: the vaccines activate key immune cells and raise PD-L1 levels on tumors.

However, there is a fault in the study: it focuses on a single vaccine type and doesn’t directly test personalized cancer vaccines. The long-term effects and particular timing of vaccination for immunotherapy also remain unclear.

In future investigations, study authors suggest exploring other ready-to-use RNA treatments to help the immune system fight cancer, boost natural immune responses and see how regular vaccinations could improve cancer treatment results.