Beta-1, 6 glucan converts tumor-associated macrophages into an M1-like phenotype. (1st November 2020) - Cheng, Hairong
Highlights: A β-D-(1→6) glucan converts M2-like macrophages to M1-like phenotype. The converting effect is mediated by Akt/NF-κB and MAPK via TLR2 receptor. β-1, 6-glucan inhibits colon cancer cell growth via its macrophage converting effect. Abstract: Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. We have reported that the β-D-(1→6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the β-1, 6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo . On a cellular mechanistic level, the β-1, 6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-κB and MAPK. Further, TLR2 was identified as the receptor of β-1, 6-glucan in the transformation effect. In addition, a very similar β-1, 6-glucan with side chains of β-Glc or α-Galρ which was purified from Lentinus edod es showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of β-1, 6-glucan in cancer immunotherapy.