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

Int J Biol Macromol. 2020 Feb 1:144:1022-1033. doi: 10.1016/j.ijbiomac.2019.09.179. Epub 2019 Oct 25.

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 demonstrated 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 decreased 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.

Keywords: Anti-tumor effect; Lachnum polysaccharide; Tumor-associated macrophages.

MeSH terms

  • Animals
  • Ascomycota / chemistry*
  • Cell Line, Tumor
  • Fungal Polysaccharides / pharmacology*
  • Humans
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Male
  • Mice
  • Phenotype*
  • RAW 264.7 Cells
  • Sarcoma / immunology*
  • Sarcoma / pathology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Toll-Like Receptor 4 / metabolism
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Fungal Polysaccharides
  • Toll-Like Receptor 4