灵芝多糖对肿瘤逃避免疫监视的拮抗作用(英文)

来源 :中国药理学与毒理学杂志 | 被引量 : 0次 | 上传用户:shanlai_lu
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Recent years,our research group focused the effects of G.polysaccharides,which are extracted from fruiting body of Ganoderma lucidum,on tumor evasion from immune surveillance.The immune system in patients with tumor often fails to control tumor growth because of deficient immunogenicity of tumor cells.Deficient major histocompatibility complex(MHC)classⅠ and costimulatory molecules on malignant cells partially results in tumor evasion since antigen bond MHC and costimulatory molecules provide two signals for T cell activation.Therefore,enhancement of MHC-Ⅰ and costimulatory molecules may favor restraint of the evasion.Our study found that G.polysaccharides can increase MHC classⅠ molecules such as H-2Kb and H-2Db as well as the costimulatory molecules B7-1 and B7-2 expression on B16F10 melanoma cells at both mRNA and protein levels,and can promote lymphocyte-mediated cytotoxicity.Tumour cells produce immune suppressive factors such as interleukin 10(IL-10),transforming growth factorβ1(TGF-β1)and vascular endothelial growth factor(VEGF)that suppress the function of immune cells or induce apoptosis of immune cells.Our study also found B16F10 cell culture supernatant(B16F10-CS)suppressed lymphocyte proliferation and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin(PHA),as well as lymphocyte proliferation in the mixed lymphocyte reaction.The suppression also associated with elevated levels of immunosuppressive IL-10,TGF-β1 and VEGF in B16F10-CS.Further,the production of IL-10,TGF-β1,and VEGF in B16F10 melanoma cells and lung carcinoma LA795 cells was suppressed by G.polysaccharides at both mRNA and protein levels.On the contrary,the production of IL-2,IFN-γand TNF-αin mononuclear lymphocytes was suppressed by B16F10-CF at both the mRNA and protein levels,whereas the suppression was ameliorated by G.polysaccharides.B16F10-CS was suppressive to the viability,phagocytic activity,NO production,TNF-αproduction and activity in peritoneal macrophages while G.polysaccharides had the antagonistic effects against this suppression.Then subsequently,the plasma of patients with lung cancer suppressed proliferation,CD69 expression,and perforin and granzyme B production in lymphocytes upon activation by PHA.However,these suppressive effects were reversed by G.polysaccharides.In conclusion,G.polysaccharides can improve the nature of B16F10 cells to activate lymphocytes and antagonize immunosuppression induced by B16F10-CS in lymphocytes and macrophages.These findings indicate that G.polysaccharides can restraint tumor evasion from immune surveillance,suggesting this potential value of G.polysaccharide to facilitate cancer immunotherapy.
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