Measuring immune peptides from immune and tumor cells during their interaction reveals treatment targets in brain cancer

Coculturing tumor cells and macrophages induced increased presentation of peptides derived from proteins associated with cytokine signaling pathways on macrophages.

• Immune checkpoint inhibitors are generally ineffective in glioblastoma due to the immunosuppressive environment created by GBM-associated macrophages.
• Cell type-specific immunopeptidome analysis revealed distinct MHC-I-associated antigens at the tumor-macrophage interface.
• Coculture systems showed elevated presentation of specific peptides linked to cytokine signaling on macrophages and Rho GTPase pathways on GBM tumor cells.
• An mRNA vaccine encoding six peptides from GAMs and GBM tumor cells was developed.
• Vaccination with two doses produced an antigen-specific immune response and significantly delayed GBM tumor growth, with some cases resulting in tumor eradication.

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