Fungal-Derived Macromolecules in Cancer and Immunomodulation: Mechanisms, Translational Pharmacology, and Therapeutic Development

Fungi are a rich source of bioactive macromolecules—including polysaccharides, proteoglycans, glycoproteins, lectins, fungal immunomodulatory proteins (FIPs), and other high-molecular-weight glycoconjugates—with emerging potential to shape immune function and influence tumor biology. These agents can modulate innate and adaptive immunity, tune inflammatory pathways, and support antitumor responses, but progress toward clinical translation depends on mechanism-first, experimentally validated pharmacology, robust material characterization, and fit-for-purpose models.

This Research Topic invites mechanistically rigorous studies on fungal-derived macromolecules (native, modified, or formulated) that connect molecular composition and structure to immune and anticancer function, and that advance candidates toward clinically relevant efficacy, safety, and developability.

We welcome contributions that:
Define immunomodulatory mechanisms of fungal macromolecules in cancer or chronic inflammatory settings, including TLR/Dectin and other PRR signaling, antigen presentation, NK/T cell activation, macrophage polarization, inflammasome tuning, and cytokine network remodeling.
Link structure to function through composition and architecture (e.g., monosaccharide linkage patterns, branching, MW distribution, glycosylation features), including structure–activity relationships for polysaccharides, glycoproteins, lectins, and FIPs.
Use advanced and translatable models, such as primary human immune cells, tumor–immune co-cultures, organoids/3D systems, microphysiological platforms, and high-content readouts (single-cell and spatial omics, multiplex cytokines, imaging).
Evaluate safety and translational readiness, including immunotoxicity, off-target immune effects, drug–drug interaction potential, and in vivo biomarkers linking immune modulation to antitumor outcomes.

Studies spanning natural product discovery, bioprospecting, and bioengineering are encouraged provided the focus remains on macromolecules and includes robust experimental pharmacology in relevant biological systems. Our aim is to showcase high-quality, reproducible science that translates fungal macromolecular therapeutics into decision-grade evidence and credible leads for oncology and immune-mediated diseases.

For manuscripts that focus on natural compounds, please utilize the ConPhyMP tool and ensure compliance with the standards outlined in the ConPhyMP statement (Front. Pharmacol. 13:953205). Additionally, compliance with the Four Pillars of Best Practice in Ethnopharmacology is mandatory. You can freely download the full version here. A comprehensive description of the studied material, including its identified source, extraction and processing methods, and clear composition, is essential.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Fungal Natural Products, Bioactive Compounds, Anticancer Drug Discovery, Immunomodulation, Inflammation, Mechanism of Action, Structure–Activity Relationships, Biosynthetic Engineering, High-Throughput Screening, AI-D, Fungal-Derived Macromolecules

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.