Lachnum polysaccharide suppresses S180 sarcoma by boosting anti-tumor immune responses and skewing tumor-associated macrophages toward M1 phenotype

Abstract Therapeutic strategies that targeting tumor-associated macrophages (TAMs) reprogramming play a crucial role in ameliorating the immunosuppressive tumor microenvironment and boosting anti-tumor immune responses. In this study, we showed that Lachnum polysaccharide (LEP) could work as an immunomodulator to reset TAMs from pro-tumor M2 to anti-tumor M1 phenotype. Mechanistically, LEP promoted Th1 polarization and the secretion of IFN-γ, which played a key role in M1 phenotype polarization. In parallel, LEP might directly activate M1 macrophages via TLR4 mediated NF-κB signaling pathway. Moreover, LEP also resulted in the accumulation of anti-tumor immune cells and decrease the infiltration of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and Treg cells, thereby potentiating anti-tumor immunity. In summary, these results revealed a novel mechanism of the anti-tumor effect of LEP and provided a potential new avenue targeting TAMs and cancer immunotherapy.