Lentinan regulates the immune efficacy of macrophage for lung metastasis in triple negative breast

[Display omitted] •Lentin (LNT) is the core component of shiitake mushroom, which has good immunomodulatory function in cancer treatment.•LNT inhibited the metastasis of the triple-negative breast tumor cells into the lungs.•LNT suppressed the polarization of the M2-type macrophages both in vitro and in vivo.•The mechanism was related to inhibiting the polarization of M2-type macrophages through JAK2/STAT3 signaling pathway. Lentinan (LNT), an immunoregulatory agent, is a compound derived from the mushroom Lentinus edodes. However, the immunological function and antitumor effect of LNT and the underlying mechanism remain poorly understood. In this study, we aimed to investigate the potential mechanism of LNT in treating TNBC lung metastasis by regulating macrophages in vivo and in vitro. In the Luc-4T1 mouse model, LNT inhibited the metastasis of the triple-negative breast cancer (TNBC) cells into the lungs. Additionally, as demonstrated by the immunohistochemical results and down-regulation of the mRNA expression of M2-type macrophage marker genes, LNT substantially inhibited IL-4-induced M2 macrophage polarization. Molecular docking and western blotting data further suggested that LNT is likely to target activation of the JAK2/STAT3 signaling pathway, and siRNA transfection experiments confirmed these findings. These results provide important implications for the use of LNT as a functional food to enhance immune function in the treatment of breast cancer.