Fungal Lectins: Emerging Glyco-Immune Checkpoint Modulators for Cancer Diagnosis, Prognosis, and Therapy

Lectins are non-immunogenic, non-enzymatic proteins distributed across microbes, fungi, plants, invertebrates, and vertebrates. Their carbohydrate-binding specificity forms the basis of diverse biomedical applications, particularly in immunomodulation, prognosis, and diagnosis. Among these, fungal lectins have gained attention as promising biomolecules, although they remain less explored than their plant and animal counterparts. Several fungal lectins, including Aleuria aurantia lectin (AAL), Laetiporus sulphureus lectin (LSL), Marasmius oreades agglutinin (MOA), Agrocybe aegerita galectin (AAG), and Rhizoctonia bataticola lectin (RBL), demonstrate unique biological activities. They regulate immune responses by influencing cytokine expression (e.g. TNF-α, IL-1β, IL-6, IL-10), act on innate and adaptive immune cells, and initiate apoptosis or necrosis via intrinsic and extrinsic pathways. Their diagnostic potential lies in recognizing aberrant glycans such as TF and Tn antigens, while their prognostic relevance is associated with monitoring glycosylation changes during cancer progression. Collectively, fungal lectins represent versatile molecules capable of serving as both functional immunomodulators and sensitive glycan-based probes. Despite extensive in vitro studies, their clinical application remains limited by insufficient in vivo validation and translational research. Advancing fungal lectins into biomedical practice requires systematic evaluation of their safety, specificity, and therapeutic potential. This review consolidates current knowledge on fungal lectins in immunomodulation, prognosis, and diagnostics, and highlights their translational prospects. Future studies should prioritize in vivo evaluation, biosensor integration, and protein engineering approaches to fully exploit fungal lectins as next-generation tools in immunotherapy and precision medicine.