Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response.

ABSTRACT: Colorectal cancer (CRC) remains refractory to most immunotherapies, with cancer vaccines failing due to an immunosuppressive tumor microenvironment. Here, we show that β-glucan-induced trained immunity overcomes these barriers by reprogramming macrophages through H3K4me3-dependent epigenetic modifications and metabolic rewiring. In female mice vaccinated with peptide-coated adenovirus-based vaccine PeptiCrad, training enhances glycolysis with creatine metabolism sustaining CXCL9/10 production, enabling macrophages to recruit NK cells via CXCR3. In turn, NK cells produce CCL5, driving cDC1 infiltration and antigen presentation, which together amplify effector memory CD8⁺ T cell responses. Moreover, with human peripheral blood mononuclear cells and CRC patient-derived organoids, trained macr

SUBMITTER: Hamdan F 

PROVIDER: S-EPMC12914026 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature