Immunomodulatory Properties of Coriolus versicolor: The Role of Polysaccharopeptide

Abstract

Traditional uses of herbal medicine have depended mostly on anecdotal evidence for much of history. The increasing application of scientific rigor to the study some of these traditional therapies in recent years has revealed potent bioactivity, notably demonstrated by the 2015 Nobel Prize for the discovery of an antimalarial compound from traditional Chinese herbs. Given the recent successes of immunotherapy and checkpoint blockade, there is a renewed interest in identifying new drugs with immunomodulatory effects. As an estimated 45-60% of cancer patients worldwide are reported to use complementary alternative medicine alongside traditional therapy, this review will highlight the literature on the immunomodulatory effects of one of these compounds. We report on the induction of a largely pro-inflammatory cytokine profile by the polysaccharopeptide (PSP) isolated from the Coriolus versicolor (Yun zhi) mushroom, as well as its effects on various immune subsets, and the clinical data that have led to its widespread adoption as an adjunct cancer therapeutic in many Eastern cultures. Particular focus is given to the potential mechanisms underlying the bioactivity of PSP and reports of its ability to promote antitumor immunity by helping overcome tolerogenic tumor microenvironments.

Keywords: Coriolus versicolor; Yun zhi; immunomodulation; mushroom; polysaccharide peptide; polysaccharopeptide.

Figure 1

Partial structure of polysaccharopeptide (PSP). PSP’s polysaccharide moiety contains a β-(1→3)-d-glucan. Figure replicated from Wan et al. (49).

Figure 2

Potential mechanisms of immuostimulatory effects of Coriolus versicolor. (A) Detection of polysaccharopeptide (PSP) by TLR(s) (and perhaps other receptors) on T lymphocytes initiates signaling cascades, such as the p38 MAPK pathway, leading to enhanced T cell proliferation and the release of largely pro-inflammatory cytokines such as IL-2 and IFN-γ. (B) Binding of PSP to any/all of Dectin-1, CR3, or TLRs on macrophages leads to the activation of genetic events that increase phagocytic activity and induces the production of oxidative radicals and cytokines such as tumor necrosis factor-α. (C) Recognition of PSP by the BCR leads to B cell activation, clonal proliferation, and eventual differentiation into IgM⁺ or IgG⁺ plasma and memory B cells. Alternatively, PSP may be acting on B cells in a similar fashion to T cells, non-specifically activating them through TLR(s) and leading to a general increase in polyclonal IgM and IgG levels (data not shown).