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Fas,又名CD95或APO-1,是细胞凋亡信号受体,通过与FasL结合诱导细胞凋亡。肿瘤细胞既可通过表达FasL的T细胞凋亡而逃逸免疫监视;又可通过cFLIP调控DISC水平,上调凋亡抑制基因及诱导Fas基因突变等抑制Fas介导的细胞凋亡。基于上述机制,可从免疫细胞层面和肿瘤细胞层面两方面调节肿瘤免疫治疗。免疫细胞抗肿瘤凋亡作用可采用激动性抗体阻断其Fas表达、FasL基因或Fas反义寡核苷酸或抗凋亡基因的转入、利用细胞因子保护作用及Caspase蛋白酶抑制剂阻断其凋亡。在肿瘤细胞方面,应用抗Fas抗体、FasL反义寡核苷酸、Fas或Bax基因转入肿瘤细胞及某些化疗药物与细胞因子等作用,增加肿瘤细胞Fas敏感性,使之容易被免疫细胞诱导凋亡。
Fas, also known as CD95 or APO-1, is a signal transducer of apoptosis and induces apoptosis by binding to FasL. Tumor cells can both escape immune surveillance through apoptosis of T cells expressing FasL, and inhibit Fas-mediated apoptosis through the regulation of DISC by cFLIP, up-regulation of apoptosis-suppressing genes and induction of Fas gene mutation. Based on the above mechanism, tumor immunotherapy can be regulated from the aspects of immune cells and tumor cells. Anti-tumor apoptosis of immune cells can be blocked by agonistic antibodies to Fas expression, FasL gene or Fas antisense oligonucleotide or anti-apoptotic gene transfer, the use of cytokine protection and Caspase protease inhibitor block Apoptosis. In tumor cells, the use of anti-Fas antibodies, FasL antisense oligonucleotides, Fas or Bax gene transfer into tumor cells and certain chemotherapeutic drugs and cytokines and other effects and increase the Fas sensitivity of tumor cells, making it easily immune cells Induces apoptosis.