| Autor: |
de Graaff P; Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands. p.degraaff.1@erasmusmc.nl.; Wageningen Food and Biobased Research, Wageningen UR, Wageningen, The Netherlands. p.degraaff.1@erasmusmc.nl., Berrevoets C; Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands., Rӧsch C; Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands., Schols HA; Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands., Verhoef K; Department of General Surgery, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands., Wichers HJ; Wageningen Food and Biobased Research, Wageningen UR, Wageningen, The Netherlands., Debets R; Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands., Govers C; Wageningen Food and Biobased Research, Wageningen UR, Wageningen, The Netherlands. coen.govers@wur.nl. |
| Abstrakt: |
Anti-cancer T-cell responses are often halted due to the immune-suppressive micro-environment, in part related to tumor-associated macrophages. In the current study, we assessed indigestible β-glucans (oatβG, curdlan, grifolan, schizophyllan, lentinan, yeast whole glucan particles (yWGP), zymosan and two additional yeast-derived β-glucans a and b) for their physicochemical properties as well as their effects on the plasticity of human monocyte-derived macrophages that were polarized with IL-4 to immune-suppressive macrophages. Beta-glucans were LPS/LTA free, and tested for solubility, molecular masses, protein and monosaccharide contents. Curdlan, yeast-b and zymosan re-polarized M(IL-4) macrophages towards an M1-like phenotype, in particular showing enhanced gene expression of CCR7, ICAM1 and CD80, and secretion of TNF-α and IL-6. Notably, differential gene expression, pathway analysis as well as protein expressions demonstrated that M(IL-4) macrophages treated with curdlan, yeast-b or zymosan demonstrated enhanced production of chemo-attractants, such as CCL3, CCL4, and CXCL8, which contribute to recruitment of monocytes and neutrophils. The secretion of chemo-attractants was confirmed when using patient-derived melanoma-infiltrating immune cells. Taken together, the bacterial-derived curdlan as well as the yeast-derived β-glucans yeast-b and zymosan have the unique ability to preferentially skew macrophages towards a chemo-attractant-producing phenotype that may aid in anti-cancer immune responses. |
Full text from SpringerLink