菇蕈多醣體對於原發位腫瘤微環境之影響

Abstract

腫瘤細胞分泌細胞激素、生長因子誘導血液中單核球向腫瘤微環境聚集，並分化為具有促進腫瘤生長之腫瘤伴隨巨噬細胞，建立適合腫瘤生長之腫瘤微環境，並引起強烈的免疫抑制反應，攻擊及破壞宿主的免疫系統，以促進腫瘤生長。本研究將探討以口服灌食給予正常小鼠及擔癌小鼠菇蕈多醣體後，對於血清、肺臟及腫瘤微環境中細胞激素、生長因子及腫瘤伴隨巨噬細胞之影響。 結果顯示，裂褶多醣體可提升正常小鼠肺臟中IFN-γ基因表現量，及降低COX-2基因表現量。在小鼠之擔癌試驗中，裂褶多醣體、靈芝多醣體可降低血清中TGF-β含量，提升腫瘤微環境中IL-12及IFN-γ基因表現量，並降低IL-6、IL-10、COX-2、TGF-β基因表現量。此外，靈芝多醣體可增加腫瘤伴隨巨噬細胞中M1巨噬細胞百分比，並降低腫瘤伴隨巨噬細胞中M2巨噬細胞百分比。 菇蕈多醣體可改變腫瘤微環境中免疫抑制性分子表現，並促使腫瘤伴隨巨噬細胞成為M1巨噬細胞，減少腫瘤伴隨巨噬細胞成為M2巨噬細胞，進而減緩腫瘤微環境之免疫抑制作用。

Cytokine and growth factor secreted by tumor cells can actively recruit blood monocytes at the tumor microenvironment, where the recruiting monocytes differentiated into tumor-associated macrophages which promote tumor progression, thereby resulting a favorable tumor microenvironment for tumor growth. The tumor microenvironment subverted the immune system and enhanced tumor growth through strong immune suppressive mechanisms within the tumor microenvironment. The current study is to investigate whether oral mushroom polysaccharides have any effect on molecular profiles within the serum, lung and tumor microenvironment and tumor-associated macrophage phenotypes. The current study showed that oral Schizophyllan treatment significantly increased IFN-γ mRNA expression, but significantly reduced COX-2 mRNA expression within the lung. For LLC1 tumor model, oral Schizophyllan or oral Ganoderma lucidum polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2 and TGF-β mRNA expression were substantially declined within the tumor microenvironment after oral Schizophyllan or oral Ganoderma lucidum polysaccharides treatments. Moreover, oral Ganoderma lucidum polysaccharides treatment significantly increased M1 phenotype of tumor-associated macrophages, but significantly reduced M2 phenotype of tumor-associated macrophages. Taken together, our study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides through altering the tumor microenvironment.