Mushroom-derived polysaccharides in cancer immunotherapy: mechanisms, human evidence, and translational priorities.

Mushroom-derived polysaccharides are widely promoted as anticancer immune modulators, but interpretation is weakened by imprecise product identity, chemically non-equivalent preparations, and extrapolation across evidence levels. This critical narrative review evaluates beta-glucans, heteropolysaccharides, polysaccharide-protein complexes, crude fractions, modified derivatives, and multicomponent extracts as preparation-specific adjunct candidates. Receptor-level evidence is strongest for general fungal beta-glucan systems, particularly Dectin-1/Syk/CARD9 signaling and conditional complement receptor 3 cooperation; direct transfer of those mechanisms to individual mushroom preparations requires product-specific causal testing. Selected animal studies support myeloid remodeling, dendritic-cell and natural-killer-cell effects, and T-cell activation, but route, exposure, product characterization, and model limitations constrain translation. Human evidence remains heterogeneous: historical randomized PSK studies reported benefit in specific adjuvant chemotherapy settings, a later phase III lentinan trial was negative for overall survival, and small maitake, Agaricus, and pleuran studies mainly report immune surrogates. Direct clinical evidence with checkpoint inhibitors, therapeutic antibodies, or cancer vaccines is not established. The field should therefore move from species-level claims to product-level development with authenticated source material, orthogonal structural analysis, contaminant control, mechanism-linked potency, route-specific pharmacokinetics, tumor pharmacodynamics, and randomized testing against contemporary standard care. Mushroom-derived polysaccharide immunomodulators remain plausible research candidates, but neither the class nor unstandardized mushroom foods or supplements are clinically validated substitutes for established cancer treatment.