ArticlePLoS computational biology2025
Biomarkers of mRNA vaccine efficacy derived from mechanistic modeling of tumor-immune interactions.
Article in PLoS computational biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Review
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Review
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Authors and funding
4 authors.
Funding
Abstract
The success of mRNA vaccines against infectious diseases such as COVID-19 has opened new avenues for their application in oncology. In cancer immunotherapy, mRNA vaccines-typically encapsulated in lipid nanoparticles (LNPs) 100-200 nm in size-enable delivery of tumor-specific antigens to activate immune responses. Here, we investigated the efficacy of mRNA vaccines in cancer by modeling tumor-immune interactions and tumor microenvironment (TME) dynamics to identify predictive biomarkers. Using a mechanistic mathematical model, we simulated tumor growth, immune cell dynamics, and vaccine pharmacokinetics in virtual cohorts of 1,635 patients generated via Latin hypercube sampling. Our simulations demonstrated a 45% average tumor size reduction and a 60% increase in CD8 + T cell infiltration in responsive tumors. Multiple regression analyses validated the predictive power of both pre- and on-treatment biomarkers. Key predictors of vaccine efficacy included antigen-presenting cell (APC) density and cytotoxic T cell fraction. Specifically, an APC density above 500 cells/mm³ in lymph nodes correlated with a 55% increase in vaccine response rates, while a cytotoxic T cell fraction above 20% in tumors was associated with a 60% reduction in tumor volume. A reduced M2/M1 macrophage ratio further improved treatment outcomes by 50%, highlighting the role of reprograming immunosuppressive macrophages. TME characteristics significantly influenced vaccine efficacy. Low extracellular matrix (ECM) density-modeled as a 5-10 × increase in hydraulic conductivity-combined with medium cytokine levels (IL-2 and TNF-α at 10-50 pg/ml), created optimal conditions for immune activation. Under these conditions, vaccine uptake improved by 35% and cytotoxic T cell infiltration increased by 65%, resulting in up to a 50% improvement in therapeutic outcomes. Model predictions aligned with pre-clinical data from melanoma and breast cancer models. These findings provide a framework for optimizing mRNA vaccine strategies and advancing personalized cancer immunotherapy.
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Registered trials
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