Table Info

Table 1.

Biological activity of most relevant β-glucans investigated in pre-clinical studies

Pre-clinical study (ref.)	Treatment models	β-glucans/fungus	Biological activity
Sorimachi K, et al., [64] Niu YC, et al., [65]	Animal model (rat bone marrow) Animal model (mouse S180 cells), IV administration	Glucan/Agaricus blazei Murill	- ↑ secretion of IL-8 and TNF-α by macrophages - ↑ production of IL-23, IL-12, IL-1 - ↑ cytokine and leukocyte growth factor production
Kubala L, et al., [66] Zhong K, et al., [67]	Human model Mice splenic Lymphocytes	Schizophyllan/Schizophyllum commune	- ↑ lymphocytes proliferation, through production of IL-2 - ↑ production of pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha
Yang A, et al., [68]	Murine macrophages Human hepatoma HepG2 cells	TPG-1/Trametes robiniophila	- ↑ production of TNF-α and IL-6 through toll-like receptor 4 (TLR4)
Wang J, et al., [69] Wang SY, et al., [70] Chien CM, et al., [71]	Animal model, in vitro, Raw 264.7 cells Human myeloid leukemia cell lines Human umbilical cord blood	Proteoglycan fraction/Ganoderma lucidum	- ↑ anti-inflammation activity against lipopolysaccharide (LPS) stimulation - ↑ T cells activity - ↑ expression of IL-1, IL-2, IL-6, TNF-α and INF-γ - modulate NK cell cytotoxicity
Carmona EM, et al., [72] Ali MF, et al., [73]	Rat cells Human model	Glucan/Pneumocystis and Aspergillus	- ↑ TNF-α, IL-6 and IL-8 production by B-lymphocytes - ↑ IL-23 and IL-6 release by dendritic cells - ↑ secretion of IL-17 and IL-22, both Th17-produced cytokines
Kankkunen P, et al., [52] Ding J, et al., [74] Vetvicka V, et al., [47]	Human macrophages Human monocyte-derived DCs Murine melanoma B16 cell line	Glucan/Saccharomyces cerevisiae	- ↑ Th2 immune response and inhibits Th1 by promoting the release of anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF-β) - ↑ IL-1β transcription and secretion - ↑ IL12, IL-2, TNF, IFN production - ↑ tumor-specific CTL activity - modulate NK cells activity and killing towards tumor cells
Ina K, et al., [75]	Human model (gastric cancer patients), IV administration	Lentinan/Lentinula edodes	- ↑ PD-L1 tumor expression - ↑ release of TNF-α, IL-12 and IFN-γ - ↑ T cells activity, especially CD8⁺ cells and Th1 polarization
Masuda Y, et al., [76] Masuda Y, et al., [77]	Animal model Animal model	Maitake α-glucan (YM-2A)/Grifola frondosa	- ↑ activation of dendritic cells and macrophages - ↑ IFN-γ production by CD4⁺ and CD8⁺ T cells
Bose N, et al., [78]	Human serum	Imprime PGG/Saccharomyces cerevisiae	- ↑ phenotypic and functional activation of monocytes - ↑ activation of neutrophils, through production of IL-8, CCL2, and CD11b

Declarations

Author contributions

VC, NR and FT contributed to literature research and article’s selection. VC, NR, FT and FM wrote the manuscript and generated the figures and tables. FM and RB contributed to the revisions of the manuscript. All authors approved the published version of the manuscript.

Conflict of interest

All authors declare that there are no conflicts of interest.

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Not applicable.

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References

Hoenigl M, Lin J, Finkelman M, Zhang Y, Karris MY, Letendre SL, et al. Glucan rich nutrition does not increase gut translocation of β-glucan. Mycoses. 2021;64:24–9. [DOI] [PubMed] [PMC]

Ooi VE, Liu F. Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem. 2000;7:715–29. [DOI] [PubMed]

Ren L, Perera C, Hemar Y. Antitumor activity of mushroom polysaccharides: a review. Food Funct. 2012;3:1118–30. [DOI] [PubMed]

Jaskari J, Kontula P, Siitonen A, Jousimies-Somer H, Mattila-Sandholm T, Poutanen K. Oat β-glucan and xylan hydrolysates as selective substrates for Bifidobacterium and Lactobacillus strains. Appl Environ Microbiol. 1998;49:175–81. [DOI]

Drzikova B, Dongowski G, Gebhardt E. Dietary fibre-rich oat-based products affect serum lipids, microbiota, formation of short-chain fatty acids and steroids in rats. Br J Nutr. 2005;94:1012–25. [DOI] [PubMed]

Snart J, Bibiloni R, Grayson T, Lay C, Zhang H, Allison GE, et al. Supplementation of the diet with high-viscosity β-glucan results in enrichment for lactobacilli in the rat cecum. Appl Environ Microbiol. 2006;72:1925–31. [DOI] [PubMed] [PMC]

Mitsou EK, Turunen K, Anapliotis P, Zisi D, Spiliotis V, Kyriacou A. Impact of a jelly containing short-chain fructo-oligosaccharides and Sideritis euboea extract on human faecal microbiota. Int J Food Microbiol 2009;135:112–7. [DOI] [PubMed]

Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E. Effects of β-glucans on the immune system. Medicina (Kaunas). 2007;43:597–606. [PubMed]

Legentil L, Paris F, Ballet C, Trouvelot S, Daire X, Vetvicka V, et al. Molecular interactions of β-(1→3)-glucans with their receptors. Molecules. 2015;20:9745–66. [DOI] [PubMed] [PMC]

10.

Brown GD, Gordon S. Immune recognition. A new receptor for β-glucans. Nature. 2001;413:36–7. [DOI]

11.

Behall KM, Scholfield DJ, Hallfrisch J. Lipids significantly reduced by diets containing barley in moderately hypercholesterolemic men. J Am Coll Nutr. 2004;23:55–62. [DOI] [PubMed]

12.

De Angelis M, Montemurno E, Vannini L, Cosola C, Cavallo N, Gozzi G, et al. Effect of whole-grain barley on the human fecal microbiota and metabolome. Appl Environ Microbiol. 2015;81:7945–56. [DOI] [PubMed] [PMC]

13.

Tong LT, Zhong K, Liu L, Zhou X, Qiu J, Zhou S. Effects of dietary hull-less barley β-glucan on the cholesterol metabolism of hypercholesterolemic hamsters. Food Chem. 2015;169:344–9. [DOI] [PubMed]

14.

Chen J, Raymond K. β-glucans in the treatment of diabetes and associated cardiovascular risks. Vasc Health Risk Manag. 2008;4:1265–72. [DOI] [PubMed] [PMC]

15.

Tappy L, Gugolz E, Würsch P. Effects of breakfast cereals containing various amounts of β-glucan fibers on plasma glucose and insulin responses in NIDDM subjects. Diabetes Care. 1996;19:831–4. [DOI] [PubMed]

16.

Pick ME, Hawrish ZJ, Gee MI, Toth E, Garg ML, Hardin RT. Oat bran concentrate bread products improve long-term control of diabetes: a pilot study. J Am Diet Assoc. 1996;96:1254–61. [DOI] [PubMed]

17.

Theuwissen E, Mensink RP. Water-soluble dietary fibers and cardiovascular disease. Physiol Behav. 2008;94:285–92. [DOI] [PubMed]

18.

Ouyang J, Isnard S, Lin J, Fombuena B, Chatterjee D, Wiche Salinas TR, et al. Daily variations of gut microbial translocation markers in ART-treated HIV-infected people. AIDS Res Ther. 2020;17:15. [DOI] [PubMed] [PMC]

19.

Ramendra R, Isnard S, Mehraj V, Chen J, Zhang Y, Finkelman M, et al. Circulating LPS and (1→3)-β-D-glucan: a folie à deux contributing to HIV-associated immune activation. Front Immunol. 2019;10:465. [DOI] [PubMed] [PMC]

20.

Mehraj V, Ramendra R, Isnard S, Dupuy FP, Ponte R, Chen J, et al. Circulating (1→3)-β-D-glucan is associated with immune activation during human immunodeficiency virus infection. Clin Infect Dis. 2020;70:232–41. [DOI] [PubMed] [PMC]

21.

Hoenigl M. Fungal translocation: a driving force behind the occurrence of non-AIDS events? Clin Infect Dis. 2020;70:242–4. [DOI] [PubMed] [PMC]

22.

Malyarenko OS, Usoltseva RV, Zvyagintseva TN, Ermakova SP. Laminaran from brown alga Dictyota dichotoma and its sulfated derivative as radioprotectors and radiosensitizers in melanoma therapy. Carbohydre Polym. 2019;206:539–47. [DOI]

23.

Geraldelli D, Ribeiro MC, Medeiros TC, Comiran PK, Martins KO, Oliveira MF, et al. Botryosphaeran, a (1→3) (1→6)-β-D-glucan, reduces tumor development and cachexia syndrome in obese male rats by increasing insulin sensitivity and FOXO3a activity. Int J Biol Macromol. 2020;165:985–94. [DOI] [PubMed]

24.

Vetvicka V, Vashishta A, Saraswat-Ohri S, Vetvickova J. Immunological effects of yeast- and mushroom-derived β-glucans. J Med Food. 2008;11:615–22. [DOI] [PubMed]

25.

Sarangi I, Ghosh D, Bhutia SK, Mallick SK, Maiti TK. Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int Immunopharmacol. 2006;6:1287–97. [DOI] [PubMed]

26.

Matsui K, Kodama N, Nanba H. Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis. Cancer Lett. 2001;172:193–8. [DOI] [PubMed]

27.

Zhang M, Kim JA, Huang AY. Optimizing tumor microenvironment for cancer immunotherapy: β-glucan-based nanoparticles. Front Immunol. 2018;9:341. [DOI] [PubMed] [PMC]

28.

Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97. [DOI] [PubMed]

29.

Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125:S33–40. [DOI] [PubMed]

30.

Dominguez-Andres J, Netea MG. Long-term reprogramming of the innate immune system. J Leukoc Biol. 2019;105:329–38. [DOI] [PubMed]

31.

Netea MG, Giamarellos-Bourboulis EJ, Domínguez-Andrés J, Curtis N, van Crevel R, van de Veerdonk FL, et al. Trained Immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection. Cell. 2020;181:969–77. [DOI] [PubMed] [PMC]

32.

Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23:89–100.e5. [DOI] [PubMed]

33.

Oba K, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Anticancer Res. 2009;29:2739–45. [PubMed]

34.

Nakano H, Namatame K, Nemoto H, Motohashi H, Nishiyama K, Kumada K. A multi-institutional prospective study of lentinan in advanced gastric cancer patients with unresectable and recurrent diseases: effect on prolongation of survival and improvement of quality of life. Kanagawa Lentinan Research Group. Hepatogastroenterology. 1999;46:2662–8. [PubMed]

35.

Cheung NK, Modak S, Vickers A, Knuckles B. Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol Immunother. 2002;51:557–64. [DOI] [PubMed]

36.

Yin X, Ying J, Li L, Zhang H, Wang H. A meta-analysis of lentinan injection combined with chemotherapy in the treatment of non small cell lung cancer. Indian J Cancer. 2015;52 Suppl 1:e29–31. [DOI] [PubMed]

37.

Liu J, Gunn L, Hansen R, Yan J. Combined yeast-derived β-glucan with anti-tumor monoclonal antibody for cancer immunotherapy. Exp Mol Pathol. 2009;86:208–14. [DOI] [PubMed] [PMC]

38.

Chen J, Seviour R. Medicinal importance of fungal β-(1→3), (1→6)-glucans. Mycol Res. 2007;111:635–52. [DOI] [PubMed]

39.

Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000;5:4–27. [PubMed]

40.

Chan GC, Chan WK, Sze DM. The effects of β-glucan on human immune and cancer cells. J Hematol Oncol. 2009;2:25. [DOI] [PubMed] [PMC]

41.

Vos AP, M’Rabet L, Stahl B, Boehm G, Garssen J. Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates. Crit Rev Immunol. 2007;27:97–140. [DOI] [PubMed]

42.

Wang N, Liu H, Liu G, Li M, He X, Yin C, et al. Yeast β-D-glucan exerts antitumour activity in liver cancer through impairing autophagy and lysosomal function, promoting reactive oxygen species production and apoptosis. Redox Biol. 2020;32:101495. [DOI] [PubMed] [PMC]

43.

Vetvicka V, Vetvickova J. Natural immunomodulators and their stimulation of immune reaction: true or false? Anticancer Res. 2014;34:2275–82. [PubMed]

44.

Li B, Cai Y, Qi C, Hansen R, Ding C, Mitchell TC, et al. Orally administered particulate β-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer. Clin Cancer Res. 2010;16:5153–64. [DOI] [PubMed] [PMC]

45.

Liu M, Luo F, Ding C, Albeituni S, Hu X, Ma Y, et al. Dectin-1 activation by a natural product β-glucan converts immunosuppressive macrophages into an M1-like phenotype. J Immunol. 2015;195:5055–65. [DOI] [PubMed] [PMC]

46.

Albeituni SH, Ding C, Liu M, Hu X, Luo F, Kloecker G, et al. Yeast-derived particulate β-glucan treatment subverts the suppression of myeloid-derived suppressor cells (MDSC) by inducing polymorphonuclear MDSC apoptosis and monocytic MDSC differentiation to APC in cancer. J Immunol. 2016;196:2167–80. [DOI] [PubMed] [PMC]

47.

Vetvicka V, Vetvickova J. Glucan supplementation has strong anti-melanoma effects: role of NK cells. Anticancer Res. 2015;35:5287–92. [PubMed]

48.

Kalafati L, Kourtzelis I, Schulte-Schrepping J, Li X, Hatzioannou A, Grinenko T, et al. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020;183:771–85.e12 [DOI] [PubMed] [PMC]

49.

Herre J, Gordon S, Brown GD. Dectin-1 and its role in the recognition of β-glucans by macrophages. Mol Immunol. 2004;40:869–76. [DOI] [PubMed]

50.

Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 2006;6:33–43. [DOI] [PubMed]

51.

Reid DM, Gow NA, Brown GD. Pattern recognition: recent insights from Dectin-1. Curr Opin Immunol. 2009;21:30–7. [DOI] [PubMed] [PMC]

52.

Kankkunen P, Teirilä L, Rintahaka J, Alenius H, Wolff H, Matikainen S. (1,3)-β-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J Immunol. 2010;184:6335–42. [DOI] [PubMed]

53.

Ariizumi K, Shen GL, Shikano S, Kumamoto T, Edelbaum D, Morita A, et al. Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. J Biol Chem. 2000;275:20157–67. [DOI] [PubMed]

54.

Thornton BP, Vĕtvicka V, Pitman M, Goldman RC, Ross GD. Analysis of the sugar specificity and molecular location of the β-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol. 1996;156:1235–46. [PubMed]

55.

Hong F, Yan J, Baran JT, Allendorf DJ, Hansen RD, Ostroff GR, et al. Mechanism by which orally administered β-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol. 2004;173:797–806. [DOI] [PubMed]

56.

O’Brien XM, Heflin KE, Lavigne LM, Yu K, Kim M, Salomon AR, et al. Lectin site ligation of CR3 induces conformational changes and signaling. J Biol Chem. 2012;287:3337–48. [DOI] [PubMed] [PMC]

57.

Sato T, Iwabuchi K, Nagaoka I, Adachi Y, Ohno N, Tamura H, et al. Induction of human neutrophil chemotaxis by Candida albicans-derived β-1,6-long glycoside side-chain-branched β-glucan. J Leukoc Biol. 2006;80:204–11. [DOI] [PubMed]

58.

Tsikitis VL, Martin A, Albina J, Reichner J. Ligation of the lactosylceramide receptor (CDw17) promotes neutrophil migration. J Am Coll Surg. 2004;199:44. [DOI]

59.

Hahn PY, Evans SE, Kottom TJ, Standing JE, Pagano RE, Limper AH. Pneumocystis carinii cell wall β-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. J Biol Chem. 2003;278:2043–50. [DOI] [PubMed]

60.

Evans SE, Hahn PY, McCann F, Kottom TJ, Pavlovic’ ZV, Limper AH. Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-kappaB-dependent mechanisms. Am J Respir Cell Mol Biol. 2005;32:490–7. [DOI] [PubMed] [PMC]

61.

Nakayama H, Yoshizaki F, Prinetti A, Sonnino S, Mauri L, Takamori K, et al. Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated neutrophil phagocytosis of nonopsonized microorganisms. J Leukoc Biol. 2008;83:728–41. [DOI] [PubMed]

62.

Li SS, Ogbomo H, Mansour MK, Xiang RF, Szabo L, Munro F, et al. Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida. Nat Commun. 2018;9:751. [DOI] [PubMed] [PMC]

63.

Vera J, Fenutría R, Cañadas O, Figueras M, Mota R, Sarrias M, et al. The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome. Proc Natl Acad Sci U S A. 2009;106:1506–11. [DOI] [PubMed] [PMC]

64.

Sorimachi K, Akimoto K, Ikehara Y, Inafuku K, Okubo A, Yamazaki S. Secretion of TNF-α, IL-8 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. Cell Struct Func. 2001;26:103–8.

65.

Niu YC, Liu JC, Zhao XM, Wu XX. A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo. Oncol Rep. 2009;21:145–52. [PubMed]

66.

Kubala L, Frankova J, Nickova K, Sandula J, Ciz M, Lojek A. The effect of (1→3)-β-D-glucans, carboxymethylglucan and schizophyllan on human leukocytes in vitro. Carbohydr Res, 2003;338: 2835–40. [DOI] [PubMed]

67.

Zhong K, Tong L, Liu L, Zhou X, Liu X, Zhang Q, et al. Immunoregulatory and antitumor activity of schizophyllan under ultrasonic treatment. Int J Biol Macromol, 2015;80:302–8. [DOI] [PubMed]

68.

Yang A, Fan H, Zhao Y, Chen X, Zhu Z, Zha X, et al. An immune-stimulating proteoglycan from the medicinal mushroom Huaier up-regulates NF-κB and MAPK signaling via Toll-like receptor 4. J Biol Chem. 2019;294:2628–41. [DOI] [PubMed] [PMC]

69.

Wang J, Yuan Y, Yue T. Immunostimulatory activities of β-D-glucan from Ganoderma lucidum. Carbohydr Polym. 2014;102:47–54. [DOI] [PubMed]

70.

Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS, et al. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer. 1997;70:699–705. [DOI] [PubMed]

71.

Chien CM, Cheng JL, Chang WT, Tien MH, Tsao CM, Chang YH, et al. Polysaccharides of Ganoderma lucidum alter cell immunophenotypic expression and enhance CD56+ NK-cell cytotoxicity in cord blood. Bioorg Med Chem. 2004;12:5603–9. [DOI] [PubMed]

72.

Carmona EM, Kottom TJ, Hebrink DM, Moua T, Singh R, Pagano RE, et al. Glycosphingolipids mediate pneumocystis cell wall β-glucan activation of the IL-23/IL-17 axis in human dendritic cells. Am J Respir Cell Mol Biol. 2012;47:50–9. [DOI] [PubMed] [PMC]

73.

Ali MF, Driscoll CB, Walters PR, Limper AH, Carmona EM. β-Glucan-Activated human B lymphocytes participate in innate immune responses by releasing proinflammatory cytokines and stimulating neutrophil chemotaxis. J Immunol. 2015;195:5318–26. [DOI] [PubMed] [PMC]

74.

Ding J, Feng T, Ning Y, Li W, Wu Q, Qian K, et al. β-Glucan enhances cytotoxic T lymphocyte responses by activation of human monocyte-derived dendritic cells via the PI3K/AKT pathway. Hum Immunol. 2015;76:146–54. [DOI] [PubMed]

75.

Ina K, Kanda M, Yoneda M, Kodera Y, Kabeya M, Yuasa S, et al. A shiitake mushroom β-Glucan, stimulates tumor-specific adaptive immunity through PD-L1 down-regulation in gastric cancer cells. Med Chem. 2016;6:710–4.

76.

Masuda Y, Nakayama Y, Tanaka A, Naito K, Konishi M. Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor. PLoS One. 2017;12:e0173621. [DOI] [PubMed] [PMC]

77.

Masuda Y, Nakayama Y, Mukae T, Tanaka A, Naito K, Konishi M. Maturation of dendritic cells by maitake α-glucan enhances anti-cancer effect of dendritic cell vaccination. Intl Immunopharmacol. 2019;67: 408–16. [DOI]

78.

Bose N, Chan AS, Guerrero F, Maristany CM, Qiu X, Walsh RM, et al. Binding of soluble yeast β-Glucan to human neutrophils and monocytes is complement-dependent. Front Immunol. 2013;4:230. [DOI] [PubMed] [PMC]

79.

Qi C, Cai Y, Gunn L, Ding C, Li B, Kloecker G, et al. Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived β-glucans. Blood. 2011;117:6825–36. [DOI] [PubMed] [PMC]

80.

Jonas A, Qiu X, Chan A, McMurray D, Bose N. Imprime PGG, a yeast β-glucan immunomodulator, can engage Fc gamma receptor (FcγR) in addition to complement receptor 3 (CR3) on human neutrophils and monocytes (abstract). In: Keystone Symposium on Tumor Immunology, Multidisciplinary Science Driving Combination Therapy; USA. Eagan, MN: Biothera; 2015.

81.

Leonardo SM, Fulton RB, Wurst LR, Gorden KB, Bykowski Jonas A, Qui X, et al. Imprime PGG binds to neutrophils through complement, Fc, and dectin-1 receptors, priming these cells for enhanced ROS production and tumor cell cytotoxicity. Cancer Immunol Res. 2016;4 Suppl 1:Abstract nr A160. [DOI]

82.

Li B, Allendorf DJ, Hansen R, Marroquin J, Ding C, Cramer DE, et al. Yeast β-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol. 2006;177:1661–9. [DOI] [PubMed]

83.

Chan AS, Jonas AB, Qiu X, Ottoson NR, Walsh RM, Gorden KB, et al. Imprime PGG-mediated anti-cancer immune activation requires immune complex formation. PLoS ONE. 2016;11:e0165909. [DOI] [PubMed] [PMC]

84.

Bose N, Ottoson NR, Qiu X, Harrison B, Lowe JR, Uhlik MT, et al. Immune pharmacodynamic responses of the novel cancer immunotherapeutic Imprime PGG in healthy volunteers. J Immunol. 2019;202:2945–56. [DOI] [PubMed]

85.

Chan A, Qiu X, Jonas AB, Patchen ML, Bose N. Imprime PGG, a yeast β-glucan immunomodulator, has the potential to repolarize human monocyte-derived M2 macrophages to M1 phenotype. J Immunother Cancer. 2014;2 Suppl 3:P191. [DOI]

86.

Chan A, Qiu X, Jonas A, Kangas T, Ottoson N, Bose N. Imprime PGG modulates the function of monocyte-derived M2 macrophages and dendritic cells to drive T cell expansion (abstract). Cancer Res. 2015;75 Suppl 15:LB225. [DOI]

87.

Fraser K, Ottoson N, Qiu X, Chan A, Jonas A, Kangas T, et al. Imprime PGG modulates the myeloid component of the tumor microenvironment to coordinate an anti-tumor immune response (abstract). 2016;76 Suppl 3:A02. [DOI]

88.

Bose N, Chan A, Jonas A, Qiu X, Ottoson N, Kangas T, et al. Imprime PGG treatment elicits a coordinated antitumor immune response that triggers enhanced expression of PD-L1 on tumor cells as well as monocyte-derived macrophages and dendritic cells (abstract). Cancer Res. 2015;75 Suppl 15:LB-228. [DOI]

89.

Fraser KA, Kangas T, Fulton RB. Imprime PGG, a soluble yeast β-glucan PAMP, enhancement of anti-tumor responses in combination with tumor targeting antibody is highly dependent on NK cell killing (abstract). Cancer Res. 2018;78 Suppl 13:3767. [DOI]

90.

Leonardo S, Gorden K, Fulton R, Wurst L. Imprime PGG decreases regulatory T cell suppression and enhances T cell proliferation and differentiation revealing additional mechanisms for its anti-tumor activity (abstract). Cancer Res. 2015;78 Suppl 15:5034. [DOI]

91.

Fulton R, Leonardo S, Michel K, Danielson M, Gorden K, Graff J. Imprime PGG, a soluble β-glucan, binds to and activate dendritic cells resulting in enhanced T cell priming, expansion, and cytokine production (abstract). Cancer Res. 2016;4 Suppl 1:B019. [DOI]

92.

Fraser K, Chan A, Fulton R, Leonardo S, Jonas A, Qiu X, et al. Imprime PGG triggers PD-L1 expression on tumor and myeloid cells and prevents tumor establishment in combination with αPD-L1 treatment in vivo (abstract). Cancer Res. 2016;76 Suppl 14:2335. [DOI]

93.

Qiu X, Chan A, Jonas A, Kangas T, Ottoson N, Graff J, et al. Imprime PGG, a yeast β-glucan PAMP elicits a coordinated immune response in combination with anti-PD1 antibody. J Immunol. 2016;196 Suppl 1:214–6.

94.

Fulton R, Leonardo S, Jonas A, Fraser K, Chan A, Ottoson N, et al. Imprime PGG, a β-glucan PAMP (pathogen-associated molecular pattern), effectively elicits in vivo maturation of antigen-presenting cells in mice and humans, suggesting potential synergy with checkpoint inhibitor therapy (abstract). Cancer Res. 2016;76 Suppl 14:LB-089, [DOI]

95.

Hong F, Hansen RD, Yan J, Allendorf DJ, Baran JT, Ostroff GR, et al. B-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res. 2003;63:9023–31. [PubMed]

96.

Halstenson CE, Shamp T, Gargano MA, Walsh RM, Patchen ML. Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3-1,6 β glucan pathogen associated molecular pattern, in healthy volunteer subjects. Invest New Drugs. 2016;34:202–15. [DOI] [PubMed] [PMC]

97.

Iglesias JL, Prathikanti R, Ma B, Mattson P, Kedrowski D, Lowe J, et al. A multicenter, open-label, phase 2 study of imprime PGG & pembrolizumab in subjects with adv squamous cell carcinoma of H&N (SCCHN) who failed pembro monotherapy or experiencing SD following completion of 4 to 8 cycles of pembro monotherapy. J Clin Oncol. 2017;35:TPS3105.

98.

Uhlik M, Bose N, Cox J, Mattson P, Gargano M, O’Day S, et al. Response and clinical benefit assessment of the combination of the dectin-1 agonist imprime PGG and anti-PD-1 pembrolizumab in chemotherapy-resistant metastatic triple negative breast cancer (TNBC) (abstract). Cancer Res. 2020;80 Suppl 4:PD1-02.

99.

Chan A, Bose N, Ottoson N, Qiu X, Harrison B, Walsh R. Clinical benefit potentially evident with immunopharmacodynamic responses in prior-checkpoint failed metastatic melanoma patients treated with imprime PGG and pembrolizumab (abstract). JITC. 2020;8:P862. [DOI]

100.

Modak S, Kushner BH, Kramer K, Vickers A, Cheung IY, Cheung NK. Anti-GD2 antibody 3F8 and barley-derived (1→3), (1→4)-β-D-glucan: a phase I study in patients with chemoresistant neuroblastoma. Oncoimmunology. 2013;2:e23402. [DOI] [PubMed] [PMC]

101.

Kushner BH, Cheung IY, Modak S, Kramer K, Ragupathi G, Cheung NK. Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res. 2014;20:1375–82. [DOI] [PubMed] [PMC]

102.

A phase Ib/II study of anti-PD-1 antibody pembrolizumab and imprime PGG for patients with metastatic non-small cell lung cancer after progression on first-line therapy: big ten cancer research consortium BTCRC-LUN15-017. [Internet]. Bethesda (MD): National Library of Medicine (US); c2016 [updated 2021 Jan 27; cited 2020 Apr 20]. ClinicalTrials.gov Identifier: NCT03003468. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03003468

103.

A phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (morpheus-CRC). [Internet]. Bethesda (MD): National Library of Medicine (US); c2018 [updated 2021 Jan 27; cited 2020 Apr 20]. ClinicalTrials.gov Identifier: NCT03555149. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03555149

104.

Winer E, Dang T, Karantza V, Su SC. KEYNOTE-119: a randomized phase III study of single-agent pembrolizumab (MK-3475) vs. single-agent chemotherapy per physician’s choice for metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2016;34:TPS1102. [DOI]

105.

Hurley PJ, Bose N, Jha G, Gargano M, Ottoson N, Gorden K, et al. Immunoglobulin restores immune responses to BTH1677 in patients with low levels of antibodies to β-glucan. Anticancer Res. 2020;40:1467–73. [DOI] [PubMed]