Do mRNA COVID–19 vaccines enhance the efficacy of anti–PD-(L)1 therapies?

Immune checkpoint inhibitors (particularly anti-PD-(L)1 agents) have been used for about a decade in the treatment of various types of cancer. They have led to improved patient survival.

Recent research suggests that certain external immune stimuli could enhance their efficacy by boosting the immune response. A study in a small cohort of patients with non-small cell lung cancer or melanoma was published in the journal Nature by Grippin et al. [1] It shows that receiving an mRNA vaccine against COVID–19 within 100 days before or after the start of anti–PD-(L)1 treatment was associated with a significant improvement in survival. The risk of death was reduced by 50% to 65%.

A study of 31,000 patients based on the SNDS

To assess whether this association was observed at the population level, we conducted a national study using the National Health Data System (SNDS). We included all patients who initiated anti–PD-(L)1 therapy in 2021 and 2022. They were followed through July 31, 2025. We compared patients who received an mRNA COVID-19 vaccine within 3 months before or after the start of treatment (co-exposed group) with patients who were not vaccinated during that same period (non-co-exposed group). The two groups were matched for age, sex, quarter of treatment initiation, and medical indication.

A 9% relative reduction in the immediate risk of death

We included 30,898 patients (15,449 in each group) with various cancers, primarily lung cancer, but also melanoma, head and neck cancers, kidney cancer, liver cancer, and bladder cancer. During follow-up, 67.3% of co-exposed patients died, compared with 70.5% of non-co-exposed patients, representing a 9% relative reduction in the instantaneous risk of death (weighted hazard ratio 0.91; 95% confidence interval 0.88–0.93). Similar results were observed regardless of cancer type and in various additional analyses.

Discussion

In this large national study, exposure to an mRNA COVID-19 vaccine within three months before or after the start of anti-PD-(L)1 therapy was associated with a modest improvement in survival. The magnitude of the association observed in our study is significantly weaker than that previously reported. This is likely due to differences in methods, population sizes, and patient representativeness.

Although these results are consistent with the hypothesis of an immunomodulatory effect of mRNA vaccines, the magnitude of the observed association does not appear sufficient, at this stage, to justify a change in the vaccination schedule relative to the initiation of anti-PD-(L)1 therapy. Prospective studies, particularly randomized clinical trials, will be necessary to confirm this effect and determine the optimal timing of this co–exposure.

[1] Grippin, A.J., Marconi, C., Copling, S. et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature 647, 488–497 (2025). https://doi.org/10.1038/s41586-025-09655-y