Table 3.
Immunomodulatory effects related to cancer: in vitro studies.
| Preparation | Experimental Model | Key Findings | References |
|---|---|---|---|
| PSP | Normal and LPS-stimulated rat peripheral blood mononuclear cells (PBMCs—5–300 μg/mL | Enhances mitogenic activity and attenuates the induced cytokines (interleukin (IL)-1β and IL-6) production in stimulated macrophages; increases cell proliferation and pro-inflammatory cytokines release in unstimulated (LPS-free) macrophages. | Jedrzejewski et al. 2016 [77] |
| Protein-bound polysaccharides (PBP) | Blood lymphocytes and breast cancer cells (MCF-7)—100 and 300 μg/mL | Induces proliferative response on blood lymphocytes, as well as IL-1β and IL-6 mRNA expression; temperature of 39.5 °C blocks the PBP-induced cytotoxicity against MCF-7 cells, which correlates with reduction in TNFα level; see Table 4 for in vivo effect. | Pawlikowska et al. 2016 [78] |
| PSP | Breast cancer (MCF-7) cells and blood lymphocytes—100 μg/mL | Reduces cell growth; upregulates TNF-α- expression but not IL-1β and IL-6; enhances the proliferative response of blood lymphocytes associated with IL-6 and IL-1β mRNA upregulation. | Kowalczewska et al. 2016 [79] |
| PSK—isolation of TLR2 agonist activity from soluble β-glucan fraction—labeled the soluble β-glucan with fluorescein | Uptake of the labeled β-glucan in J774A macrophages and JAWSII dendritic cells—10–1000 µg/mL | Uptake inhibited by anti-Dectin-1 antibody but not by anti-TLR2 antibody; Dectin-1 is the receptor for β-glucan; lipid fraction enhances the uptake of the soluble β-glucan. | Quayle et al. 2015 [80] |
| PSP | Peritoneal macrophages from mice—25 μg/mL | Stimulates the expressions of cytokines, as well as TLR4, TRAF6, phosphorylation of NF-κB p65 and phosphorylation of c-Jun (a component of the transcription factor AP-1) in peritoneal macrophages from C57BL/10J (TLR4+/+) mice but not from C57BL/10ScCr (TLR4−/−) mice; see Table 4 for in vivo effect. | Wang et al. 2015 [81] |
| Polysaccharides—hot water extraction in house | Mouse splenocytes—high dose of 30 mg/mL | Stimulates splenocytes proliferation; fluorescence-labeled polysaccharides selectively stained mouse B cells but not T-cells; induces the production of IgM and IgG1 with or without exogenously added IL-4; membrane Ig (B cell antigen-receptor) acts as the polysaccharide binding protein; induces B-cell proliferation (inhibited by anti-mouse immunoglobulin (Ig) blocking antibody or in cells from TLR4-mutant mice; increases the phosphorylation of ERK-1/2 and p38 MAPK; enhances the nuclear translocation of the cytosolic NF-κB p65 subunit. | Yang et al. 2015 [82] |
| PSK as TLR2 agonist | PBMCs from healthy human donors—monocyte-derived DCs and tumor fusion cells | Upregulates MHC (class II and CD86) expression on DC/tumor; increases fusion efficiency; increases production of fusions derived IL-12p70; activates CD4+ and CD8+ T-cells to induce IFN-γ production; enhances induction of CTL activity specific for Mucin 1. | Koido et al. 2013 [83] |
| PSK | Mouse bone marrow-derived dendritic cells (DC)—5, 10, 20, 40, and 80 µg/mL) | Induces DC maturation—dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40; induces the production (mRNA and protein levels) of IL-12, TNF-α, and IL-6. | Engel et al. 2013 [84] |
| PSP | PBMCs—10 and 100 μg/mL | Increases monocytes counts (CD14+/CD16−) compared to controls—confirmed by CD14 and MHCII antibodies; no significant effect on proliferation of T-cells, NK, and B-cells. | Sekhon et al. 2013 [85] |
| Purified new protein—YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide | Mice lymphocyte proliferation—20 μg/mL | Induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; specifically triggers the differentiation of CD1d+ B cells into IL-10-producing regulatory B cells (Bregs); enhances the expression of CD1d; activates Breg function via interaction with TLR2 and TLR4 and upregulation of the TLR-mediated signaling pathway. | Kuan et al. 2013 [86] |
| PSK | Human peripheral blood mononuclear cells—12–100 µg/mL | Activates NK cells to produce IFN-γ and to lyse K562 target cells; enhances trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity ADCC against SKBR3 and MDA-MB-231 breast cancer cells; effect related to both direct and IL-12-dependent (indirect) mechanism. | Lu et al. 2011 [87] |
| PSK | J774A.1 cells and primary splenocytes—125 μg/mL | Induces TNF-α and IL-6 secretion by wild-type but not by TLR4-deficient peritoneal macrophages; TNFα secretion by J774A.1 cells and primary splenocytes effect inhibited by TLR4 blocking antibody. | Price et al. 2010 [88] |
| PSP | Human PBMCs—25 μg/mL | Upregulates the expression of (e.g., IFN-γ, CXCL10, TLR4, TLR5) while downregulating (e.g., TLR9, TLR10, SARM1, TOLLIP) other genes related with TLR signaling pathway; upregulated some cytokines (GCSF, GM-CSF, IL-1α, IL-6, IFN-γ) by more than 1.3 times; increases the mRNA levels of TRAM, TRIF, and TRAF6; increases the protein level of TRAF6. | Li et al. 2010 [89] |
| PSK | B-cells—human B-cell line BALL-1—1–100 µg/mL | Enhances IgM production in B-cells. | Maruyama et al. 2009 [90] |
| Polysaccharides from New Zealand isolate (Wr-74) and a patented strain (ATCC-20545) of C. versicolor—culture medium isolates | Murine splenocytes—extracellular polysaccharide (1150 µg/mL), and intracellular polysaccharide (IPS) (100 µg/mL) | Induces cytokine production (interleukin 12 and gamma interferon) in murine splenocytes. | Cui et al. 2007 [8] |
| PSP | Human T lymphocyte proliferation—100 or 500 µg/mL | Exhibits similar and additive inhibitory effects to ciclosporin to suppress activated T-cell proliferation, Th1 cytokines; reduces CD3+/CD25+ cell expression but not Th2 cytokine expression. | Lee et al. 2008 [91] |
| Ethanol–water extract—commercial source | Proliferation of murine (BALB/c mice) splenic lymphocytes—12.5–400 μg/mL | Enhances cell proliferation by up to 2.4-fold in a time- and dose-dependent manner; upregulates Th1-related cytokines (IL-2 and IL-12); enhanced the level of Th1-related cytokines (IFN-γ and IL-18) transiently (24 h, but not at 48 and 72 h) while Th2-(IL-4 and IL-6). | Ho et al. 2004 [92] |
| PSK | Dendritic cells derived from CD14-positive cells obtained from human peripheral blood monocytes | Increases the expression of HLA (class II antigen) and CD40; increases the number and expression of CD80-, CD86- and CD83-positive cells; decreases FITC-dextran uptake; augments IL-12 production and allogeneic mixed lymphocyte reaction; induces antigen-specific cytotoxicity. | Kanazawa et al. 2004 [93] |
| PSK | Mouse peritoneal PMNs—500 µg/ml | In combination with IFN-γ, increases NO production. | Asai et al. 2000 [94] |
| PSK and fractions (F1 <50 kDa; F2 50–100 kDa; F3 100–200 kDa; F4 >200 kDa) | U937 and THP-1 cells differentiation; TNF-induced cytotoxicity in L929 cells—5–500 µg/mL | In combination with IFN-γ, increases NO production and cell differentiation; enhances cytotoxicity in L929 cells; fraction F4 is the most active. | Kim et al. 1990 [49] |
Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CTL, cytotoxic T lymphocytes; DC, dendritic cells; FITC, fluorescein isothiocyanate; HLA, human leukocyte antigen; IFN-γ, interferon-γ; LPS, lipopolysaccharides; MHC, major histocompatibility complex; PMBCs, peripheral blood mononuclear cells; PMN, polymorphonuclear cells; SARM, sterile-alpha and Armadillo motif-containing protein; TOLLIP, Toll interacting protein; TRIF, TIR domain-containing adaptor protein-inducing interferon β; TRAM, (TRIF)–related adaptor molecule; TRAF, tumor necrosis factor receptor (TNF-R)-associated factor.