Mushroom-derived Immunomodulators: Mechanistic insights, omics integration, AI innovation, and clinical applications...

Mushrooms are rich in structurally diverse bioactive compounds that exert potent immunomodulatory effects, making them promising candidates for next-generation immunotherapies. This review comprehensively examines their immunomodulatory mechanisms, emphasizing roles in both innate and adaptive immune regulation. Specifically, it explores the interactions of polysaccharides, fungal immunomodulatory proteins (FIPs), lectins, terpenoids, and phenolics with pattern recognition receptors (PRRs) on immune cells such as macrophages, dendritic cells, and natural killer cells, which subsequently trigger downstream signaling cascades that modulate cytokine production, regulate Th1/Th2 balance, and promote regulatory T cell function. By influencing these immune pathways, mushroom-derived compounds have shown significant therapeutic potential in cancer immunotherapy, infectious disease management, autoimmune modulation, and functional nutrition. Building on these findings, this review further discusses how recent advances in omics technologies and artificial intelligence (AI) could unlock deeper insights into the biosynthetic pathways, immune targets, and therapeutic mechanisms of these compounds, as well as how such tools might be harnessed to predict and optimize immunomodulatory efficacy. To address key challenges such as variability in extract composition, lack of standardized analytical methods, and limited clinical validation, this review proposes integrative strategies including the implementation of standardized extraction protocols, AI-assisted compound profiling, and omics-guided bioinformatics modeling. Collectively, these approaches aim to bridge the gap between experimental discovery and clinical translation, positioning mushrooms as precision-guided agents in next-generation immunotherapy.