COVID-19 mRNA Vaccines May Boost Immunotherapy Response in Cancer

COVID-19 vaccination may boost the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy, according to study findings published in Nature.

Researchers found that patients with advanced non-small cell lung cancer (NSCLC) or melanoma who received an mRNA COVID-19 vaccine within 100 days of starting immunotherapy lived significantly longer than those who were not vaccinated. Specifically, in the NSCLC cohort, median overall survival (OS) was 37.3 months in vaccinated patients compared with 20.6 months in unvaccinated patients (adjusted hazard ratio 0.51).

ICIs are key agents in cancer therapies, offering patients extended survival benefits. However, they can be less effective in patients without pre-existing immunity. While personalized mRNA cancer vaccines can help overcome this by directing immune attacks against specific tumor antigens, their complexity and lengthy manufacturing process limit widespread use. In this study, researchers found that mRNA vaccines developed for SARS-CoV-2 may offer a similar immune-sensitizing effect, enhancing tumor response to ICIs.

In preclinical mouse models, the authors demonstrate that mRNA vaccines targeting the SARS-CoV-2 spike protein provoke a strong type I interferon (IFN) response, which activates innate immune cells (dendritic cells and macrophages) and leads to priming of CD8+ T cells against tumor-associated antigens. Tumors that were otherwise “cold” (poorly immunogenic, with low T-cell infiltration) became responsive to ICIs when combined with the mRNA vaccine strategy.

Mechanistically, the IFN response triggered by the vaccine led to increased antigen presentation and CD8+ T-cell activation but also drove up PD-L1 expression on tumor cells, creating a condition in which checkpoint blockade became more effective.

Human data supported this model. Among 884 patients with advanced cancer treated with ICIs, 180 received an mRNA COVID-19 vaccine within 100 days of starting therapy. Of these, most received either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine, with 1 or 2 doses administered around the start of treatment.

After adjusting for 39 clinical and demographic factors, vaccinated patients had markedly better survival outcomes than unvaccinated patients. Median OS was 37.3 months among those who received a COVID-19 mRNA vaccine, compared with 20.6 months in those who did not. Three-year OS was also nearly doubled—55.7% versus 30.8%—corresponding to an adjusted hazard ratio of 0.51. These benefits were consistent across both stage 3 and 4 NSCLC, regardless of vaccine type or prior vaccination history.

Among patients with NSCLC whose baseline PD-L1 TPS was less than 1% (traditionally poor responders to ICIs), vaccinated patients had OS similar to those whose tumors had higher PD-L1 expression—suggesting that the vaccine helped “warm up” immunologically cold tumors.

Importantly, the survival advantage was unique to patients receiving ICIs, as no similar improvement was seen in patients who received chemotherapy or other vaccines, such as influenza or pneumococcal vaccines, within the same time frame. This suggests that the immune stimulation triggered by mRNA COVID-19 vaccination specifically enhances the effectiveness of checkpoint inhibition, potentially by activating interferon signaling and improving tumor antigen presentation.

The authors propose that off-the-shelf mRNA vaccines targeting non-tumor antigens (such as SARS-CoV-2 spike) could serve as universal immune modulators to sensitize tumors to ICIs—offering a more practical and broadly available alternative to personalized neoantigen-based cancer vaccines, which are complex and time-consuming to manufacture.

Further research is needed, as the authors caution that this is a retrospective, observational study in humans. Controlled prospective trials are necessary to validate causality and refine timing, dose and patient selection.

REFRENCES

Grippin A, Marconi C, Copling S, et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature. October 22, 2025. Doi:10.1038/s41586-025-09655-y