SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade
Adam Grippin, Christiano Marconi, Sage A. Copling, Nan Li, Chen Braun, Cole Woody et al. · 2025 · 125 citationsRead the paper
Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1–9. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes10–14. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for maximal efficacy in immunologically cold tumours, which respond by increasing PD-L1 expression. Similar correlates of vaccination response are found in humans, including increases in type I interferon, myeloid–lymphoid activation in healthy volunteers and PD-L1 expression on tumours. Moreover, receipt of SARS-CoV-2 mRNA vaccines within 100 days of initiating ICI is associated with significantly improved median and three-year overall survival in multiple large retrospective cohorts. This benefit is similar among patients with immunologically cold tumours. Together, these results demonstrate that clinically available mRNA vaccines targeting non-tumour-related antigens are potent immune modulators capable of sensitizing tumours to ICIs. mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.
What the full text shows
Tested in real conditions- COVID-19 mRNA vaccination within 100 days of ICI initiation significantly improved median overall survival (OS) in NSCLC patients. — 37.3 months vs. 20.6 months (Stage III/IV NSCLC patients; adjusted HR = 0.51)
- COVID-19 mRNA vaccination within 100 days of ICI initiation improved 3-year overall survival in NSCLC patients. — 55.7% vs. 30.8% (Stage III/IV NSCLC patients)
- Combination of RNA-LNPs and ICI increased PD-1 expression on total tumour-infiltrating CD8+ cells. — 51.363% vs. 2.39% (B16F0 melanoma mouse model)
- Combination therapy increased the proportion of PD-1+ CD8+ T cells within the total CD3+ T cell compartment. — 60.6% vs. 5.69% (B16F0 melanoma mouse model)
- mRNA immunization in healthy humans caused a massive surge in plasma IFNα at 24 hours. — average ~280-fold increase vs. baseline (Healthy volunteers receiving mRNA-1273)
- Combination of RNA-LNPs and ICI increased the likelihood of tumour-infiltrating lymphocytes being tetramer reactive. — 7.98% vs. 3.10% (B16F0 melanoma mouse model)
- Setup
- NSCLC cohort (n=884), melanoma cohort (n=210), mouse models (C57BL/6 and Rigi-knockout), and healthy human volunteers (n=16).
- How
- The study used retrospective cohort analysis of NSCLC and melanoma patients, preclinical mouse models (B16F0, B16F10-OVA, LLC) treated with RNA-LNPs and anti-PD-1/PD-L1, and cytokine/flow cytometry analysis of healthy human volunteers.
- Limitations
- Retrospective nature of human survival cohorts · Small sample size for healthy human volunteer cytokine kinetics · Preclinical mouse models may not fully replicate human TME complexity
Summarized by Gemma 4 from the open-access full text · 11 Oct 2026. Read it