mRNA-LNP vaccination induces microenvironment remodeling and generation of tissue-resident memory T cells in glioblastoma

mRNA-LNP vaccination in an immunocompetent EGFRvIII-driven syngeneic glioblastoma model induces durable EGFRvIII-specific immunity, achieving complete tumor eradication and long-term protection after intracranial rechallenge.

• Why it matters: Glioblastoma’s immunosuppressive microenvironment limits effective T-cell activity, and it is unclear how mRNA vaccines remodel the tumor immune ecosystem to sustain control.
• What they did: Using flow cytometry, tumor interstitial fluid profiling, multiplex immunostaining, spatial transcriptomics, and ligand-receptor modeling, the study mapped early microenvironment changes after antigen-specific mRNA-LNP vaccination.
• The result: Vaccination remodeled tumor niches by expanding pro-inflammatory, antigen-presenting myeloid cells, increasing activated cytotoxic CD8 T-cell infiltration, and strengthening interferon-responsive signaling, including CXCL16–CXCR6-centered chemokine relay networks linked to tissue residency programming.

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