Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity

• Published in: Communications biology Vol. 7; no. 1; p. 222
• Main Authors: Wold, Christian Winther, Christopoulos, Panagiotis F., Arias, Maykel A., Dzovor, Deborah Elikplim, Øynebråten, Inger, Corthay, Alexandre, Inngjerdingen, Kari Tvete
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 631/250/2504/342; 64/60; 692/4028/67/580; Agonists; Animals; Antitumor activity; Biomedical and Life Sciences; Cancer; Cancer immunotherapy; Cytokines; Fungal Polysaccharides - pharmacology; Glucans; Humans; Immunotherapy; Inflammation; Inonotus; Interleukin 6; Lectins, C-Type; Life Sciences; Macrophages; Mice; Nitric oxide; Pattern recognition receptors; Polysaccharides; TLR2 protein; TLR4 protein; Toll-Like Receptor 4; Toll-Like Receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Water; White rot; γ-Interferon
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-05853-y

Fungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate β-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages. Two water soluble polysaccharides from the white rot fungus Inonotus obliquus mount a potent anti-tumour response by inducing anti-cancer activity of macrophages, hence can be strong candidates for cancer immunotherapy.