[关键词]
[摘要]
随着免疫学技术的进步,大量肿瘤抗原不断被发现。DC摄取肿瘤抗原诱导免疫激活还是抑制,取决于肿瘤细胞释放危险信号(GMCSF、单核趋化蛋白1、MCP1及热休克蛋白等)还是抑制性信号(TGFβ、IDO和iNOS等)。在危险信号的调节下,激活Th1细胞免疫应答清除肿瘤;而在抑制性信号的作用下,激活Th2应答,不能有效清除肿瘤。肿瘤免疫治疗方面的进展主要表现在抗体疗法、T细胞疗法及肿瘤疫苗。目前至少有7种抗体与化疗药物合用的临床效果已经被证实;尽管抗不同种癌症的抗体种类在逐渐增加,但还需进一步探讨用于抗体治疗的新靶点、开发新抗体及扩大抗体应用的抗肿瘤范围。而T细胞疗法治疗效果不十分理想。大多数肿瘤疫苗处于Ⅰ期和Ⅱ临床试验,但为数不多的Ⅲ期临床试验结果不理想,尚需进一步完善。抗体在免疫监视中的重要作用被逐渐认识,肿瘤免疫预防最终可能成为现实。
[Key word]
[Abstract]
New tumor antigens are continuously being discovered due to the improvement of immunologic techniques. Whether dendritic cells induce immune activation or immune inhibition after they capture tumor antigens depends on the danger signals (GMCSF, MCP1, and HSP) or the inhibitory signals (TGFβ, IDO, and iNOS) released by tumor cells. Under the regulation of danger signals, dendritic cells activate Th1 immune response and eliminate tumors; under the regulation of inhibitory signals, they activate Th2 immune response and can not effectively eliminate tumors. Progress in tumor immunotherapy mainly is manifested by antibodybased therapy, T cellbased therapy, and tumor vaccinebased therapy. To day at least 7 antibodies have been confirmed effective when combined with chemotherapeutic agents in treatment of tumors. Despite of the progress made in antibody therapy, discovery of new targets, development of new antibodies, and expanding of the application scope to more tumors still need intensive research efforts. The clinical effects of T cellbased therapy have not been satisfactory; most tumor vaccinebased therapies are in phase Ⅰ and Ⅱ clinical trial, and the outcomes of few phase Ⅲ clinical trials are not satisfactory, leaving more work to be done for improvement. As we understand more about the roles of antibody in immune surveillance, it will help to make immunotherapy of tumors a promising strategy.
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[基金项目]
国家自然科学基金资助项目(No. 30972782);吉林省科技发展计划项目(No. 20080931)