A large retrospective study from the University of Florida and The University of Texas MD Anderson Cancer Center, published in Nature, reports that patients with advanced non-small cell lung cancer or metastatic melanoma lived significantly longer if they received a Pfizer-BioNTech or Moderna COVID-19 mRNA shot within 100 days of starting immune checkpoint inhibitors. The authors stress the findings are observational and will require confirmation in randomized trials.
Patients with stage III/IV non-small cell lung cancer (NSCLC) or metastatic melanoma who received an mRNA COVID-19 vaccine within 100 days of initiating immune checkpoint inhibitors (ICIs) had markedly improved overall survival compared with unvaccinated peers, according to a peer‑reviewed study published October 22, 2025, in Nature. The NSCLC cohort analysis included 180 vaccinated and 704 unvaccinated MD Anderson patients; receipt of an mRNA vaccine was associated with a longer median overall survival (37.3 months versus 20.6 months) and higher three‑year survival (55.7% versus 30.8%) after multivariable adjustment. A separate metastatic melanoma cohort (43 vaccinated; 167 unvaccinated) also showed substantial benefit; median survival for vaccinated patients was not reached at analysis, and three‑year survival was 67.6% versus 44.1% in the unvaccinated group. (dx.doi.org)
The survival advantage appeared specific to mRNA vaccination. In NSCLC patients starting ICIs, receipt of influenza or pneumonia vaccines within the same 100‑day window was not linked to improved longevity; similarly, COVID-19 vaccination around the start of chemotherapy (without ICIs) showed no survival effect. These analyses included sensitivity checks for timing and immortal‑time bias. (dx.doi.org)
Preclinical work in the same paper helps explain the association. In mouse models, researchers recreated a spike mRNA–lipid nanoparticle vaccine approximating BNT162b2 and combined it with ICIs; the pairing suppressed tumor growth in otherwise ICI‑resistant models. Mechanistic data indicated type I interferon–driven activation of innate and adaptive immunity and increased PD‑L1 expression on tumors, consistent with synergy with PD‑1/PD‑L1 blockade. (dx.doi.org)
Outside experts and multiple news outlets reported the findings, noting the size of the retrospective cohorts (more than 1,000 records) and the magnitude of the lung‑cancer survival difference (37.33 months versus 20.6 months). Reporters also highlighted that the melanoma cohort’s median survival among vaccinated patients had not yet been reached. (reuters.com)
UF and MD Anderson investigators emphasized that the results are preliminary. “Although not yet proven to be causal, this is the type of treatment benefit that we strive for and hope to see with therapeutic interventions — but rarely do,” said Duane Mitchell, M.D., Ph.D., director of the UF Clinical and Translational Science Institute. Co‑senior author Elias Sayour, M.D., Ph.D., called the implications “extraordinary,” suggesting the work points toward the possibility of broader, nonspecific immune‑priming strategies. (sciencedaily.com)
Next steps include a randomized clinical trial effort. UF says planning is underway within the UF‑led OneFlorida+ Clinical Research Network, which links health systems across multiple states to support large pragmatic studies. (sciencedaily.com)
Funding disclosures and conflicts were reported. UF states the study received support from the National Cancer Institute and multiple foundations. The Nature article lists competing interests including RNA‑therapeutics patents from several authors; some technologies are licensed to iOncologi Inc., and co‑senior author Sayour is a scientific advisor who receives royalties. (sciencedaily.com)
What this means now: The work strengthens the hypothesis that clinically available mRNA vaccines can act as potent, nonspecific immune modulators to sensitize tumors to ICIs. But because the evidence is observational, clinicians and patients should view the association as promising rather than practice‑changing until randomized trials test whether timing COVID‑19 mRNA vaccination around ICI initiation improves outcomes. (dx.doi.org)