articleNature CommunicationsJan 28, 2026GOLD OA

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

FHFiras HamdanSGSara GandolfiFDFederica D’AlessioYGYvonne GiannoulaJKJulia Kolikova

University of Helsinki · Helsinki University Hospital · +6 more institutions

PubMed
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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…

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Topics & keywords

Topics
Keywords
  • Colorectal cancer
  • Immunity
  • Reprogramming
  • Epigenetics
  • Immune system
  • Adjuvant
  • Peripheral blood mononuclear cell
  • Innate immune system
UN Sustainable Development Goals
  • Good health and well-being
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