Beta-1,6 glucan converts tumor-associated macrophages into an M1-like phenotype

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 beta-D-(1 -> 6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the beta-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 beta-1,6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-kappa B and MAPK. Further, TLR2 was identified as the receptor of beta-1,6-glucan in the transformation effect. In addition, a very similar beta-1,6-glucan with side chains of beta-Glc or alpha-Gal. which was purified from Lentinus edodes showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of beta-1,6-glucan in cancer immunotherapy.