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肿瘤免疫检查点抑制剂联合治疗策略及临床应用

Combination therapy strategy of tumor immune checkpoint inhibitor and its clinical application

  • 摘要: 目的:免疫检查点抑制剂(immune checkpoint inhibitions,ICIs)的应用显著改善了多种肿瘤的预后,是当前肿瘤治疗中备受重视的手段。以程序性死亡因子-1(programmed death 1,PD-1)、程序性死亡因子配体-1(programmed death ligand 1,PD-L1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte antigen 4,CTLA-4)单克隆抗体为主的免疫检查点的临床研究结果显示,单一ICIs临床效果有限。不同ICIs的联合治疗、联合化疗及联合抗肿瘤血管生成药物可明显提高疗效,新发现的免疫检查点淋巴细胞激活基因-3(lymphocyte activation gene-3,LAG-3)、T细胞免疫球蛋白黏液素3(T cell immunoglobulin mucin-3,TIM-3)、T细胞免疫球蛋白和ITIM域(T cell immunoglobulin and ITIM domain,TIGIT)等抑制剂的转化和联合应用,对难治性或ICIs耐药患者的疗效值得期待。

     

    Abstract: The implementation of immune checkpoint inhibitions (ICIs) has improved the prognosis of multiple cancers. Anti-programmed cell death 1(PD-1)/anti-programmed cell death 1 ligand 1 (PD-L1) and anti-CTLA-4 monotherapy showed the limited efficacy in clinical studies and there are unmet needs for the development of new strategy of immunotherapy. Currently, combination therapy strategies including combination of different ICIs, chemotherapy, or anti-angiogenesis agents have increased the response rate of ICIs in multiple cancers. The development of the inhibitors of novel immune checkpoint such as lymphocyte activation gene-3(LAG-3), T cell immunoglobulin mucin-3(TIM-3), and T cell immunoglobulin and ITIM domain(TIGIT) will be expected for further improving the survival of refractory cancer patients or patients who are resistant to present ICIs.

     

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