From macrofungal polysaccharides to precision microbial immunotherapy: reprogramming the tumor microenvironment through immunometabolic and gene-regulatory pathways
8 affiliations
- 1Department of Medical Laboratory Science, Kingsley Ozumba Mbadiwe University, Ogboko, Ideato, Imo, Nigeria
- 2Department of Community Medicine, Faculty of Clinical Sciences, Bayelsa Medical University, Yenagoa, Bayelsa, Nigeria
- 3Department of Microbiology, Faculty of Science, Bayelsa Medical University, Yenagoa, Bayelsa, Nigeria
- 4Department of Microbiology, Federal University Otuoke, Otuoke, Bayelsa, Nigeria
- 5Goodnight Family Department of Sustainable Development, Appalachian State University, Boone, NC, United States
- 6Department of Public Health, Faculty of Health Sciences, Bayelsa Medical University, Yenagoa, Bayelsa, Nigeria
- 7Niger-Delta Institute for Emerging and Re-emerging Infectious Diseases, Federal University Otuoke, Yenagoa, Bayelsa, Nigeria
- 8Department of Microbiology, Faculty of Natural Sciences, Hezekiah University, Umudi, Nkwerre, Imo, Nigeria
Abstract
Engineered microbial immunotherapies can localize immune-modulating signals within solid tumors, where hypoxia, suppressive myeloid cells, deficient antigen presentation, and dysfunctional T-cell trafficking often limit immunotherapy. Macrofungal polysaccharides, especially structurally defined β-glucans, offer mechanistic templates rather than interchangeable drug substances for source-specific, structure-controlled immune engineering programs. Their activity depends on linkage, branching, molecular mass, conformation, solubility, aggregation, and physical presentation. Critically, the strongest Dectin-1 and trained-immunity evidence discussed here uses particulate β-glucans from Saccharomyces cerevisiae; those findings cannot be assigned directly to macrofungal β-glucans without material-specific comparison. We therefore distinguish four engineering architectures: de novo microbial biosynthesis of a defined β-glucan, microbial surface display, delivery of a pre-characterized β-glucan cargo, and delivery of non-glycan payloads that mimic the desired downstream immune program. Because therapeutic bacteria have not yet been shown to reproduce a macrofungal β-glucan with controlled linkage, branching, conformation, and presentation, near-term development should prioritize standardized cargo delivery or pathway mimicry. In pancreatic and colorectal cancer models, yeast whole-glucan particles have altered myeloid trafficking or generated epigenetically and metabolically trained macrophages linked to CXCL9/CXCL10 production, natural killer-cell recruitment, conventional type 1 dendritic-cell accumulation, and stronger CD8 T-cell responses. Human evidence remains preliminary and cannot establish β-glucan-specific efficacy in uncontrolled combination studies. This Perspective proposes source-resolved material characterization, receptor and cell-state testing, multidimensional pharmacodynamic biomarkers, and microbial safety controls as prerequisites for translating fungal-inspired immune programs into precision cancer therapeutics.
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BibTeX
@article{dunga2026from,
title = {{From macrofungal polysaccharides to precision microbial immunotherapy: reprogramming the tumor microenvironment through immunometabolic and gene-regulatory pathways}},
author = {Kingsley Excel Dunga and Sylvester Chibueze Izah and Ebinyo Rebecca Aseibai and Matthew Chidozie Ogwu and Vivian Ibienebakabobo Promise and Nsikak Godwin Etim and Irene Nneka Ohanusi},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1966586},
url = {https://doi.org/10.3389/fonc.2026.1966586},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From macrofungal polysaccharides to precision microbial immunotherapy: reprogramming the tumor microenvironment through immunometabolic and gene-regulatory pathways
AU - Kingsley Excel Dunga
AU - Sylvester Chibueze Izah
AU - Ebinyo Rebecca Aseibai
AU - Matthew Chidozie Ogwu
AU - Vivian Ibienebakabobo Promise
AU - Nsikak Godwin Etim
AU - Irene Nneka Ohanusi
PY - 2026
DA - 2026/10/12
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1966586
UR - https://doi.org/10.3389/fonc.2026.1966586
AB - Engineered microbial immunotherapies can localize immune-modulating signals within solid tumors, where hypoxia, suppressive myeloid cells, deficient antigen presentation, and dysfunctional T-cell trafficking often limit immunotherapy. Macrofungal polysaccharides, especially structurally defined β-glucans, offer mechanistic templates rather than interchangeable drug substances for source-specific, structure-controlled immune engineering programs. Their activity depends on linkage, branching, molecular mass, conformation, solubility, aggregation, and physical presentation. Critically, the strongest Dectin-1 and trained-immunity evidence discussed here uses particulate β-glucans from Saccharomyces cerevisiae; those findings cannot be assigned directly to macrofungal β-glucans without material-specific comparison. We therefore distinguish four engineering architectures: de novo microbial biosynthesis of a defined β-glucan, microbial surface display, delivery of a pre-characterized β-glucan cargo, and delivery of non-glycan payloads that mimic the desired downstream immune program. Because therapeutic bacteria have not yet been shown to reproduce a macrofungal β-glucan with controlled linkage, branching, conformation, and presentation, near-term development should prioritize standardized cargo delivery or pathway mimicry. In pancreatic and colorectal cancer models, yeast whole-glucan particles have altered myeloid trafficking or generated epigenetically and metabolically trained macrophages linked to CXCL9/CXCL10 production, natural killer-cell recruitment, conventional type 1 dendritic-cell accumulation, and stronger CD8 T-cell responses. Human evidence remains preliminary and cannot establish β-glucan-specific efficacy in uncontrolled combination studies. This Perspective proposes source-resolved material characterization, receptor and cell-state testing, multidimensional pharmacodynamic biomarkers, and microbial safety controls as prerequisites for translating fungal-inspired immune programs into precision cancer therapeutics.
SN - 2234-943X
ER -