免疫检查点抑制剂在肿瘤治疗中的不良反应及毒性管理

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1、授予单位代码10089学号或申请号20153447中国图书分类号R730.51HebeiMedicalUniversity硕士学位论文专业学位免疫检查点抑制剂在肿瘤治疗中的不良反应及毒性管理研究生：张璐洁导师：丁翠敏教授专业：内科学二级学院：第四医院2018年3月目录中文摘要············································································································1英文摘要··

2、··········································································································2英文缩写············································································································3综述免疫检查点抑制剂在肿瘤治疗中的不良反应及毒性管理·······

3、·········4致谢··················································································································24个人简历··········································································································25中文摘要免疫检查点抑制剂在

4、肿瘤治疗中的不良反应及毒性管理摘要近几年，免疫检查点抑制剂（immunecheckpointinhibitors，ICPi）已成为多种晚期癌症的标准治疗方法。这些药物主要针对的靶点包括细胞毒性T淋巴细胞相关抗原4（cytotoxicTlymphocyte-associatedantigen4，CTLA-4），程序性死亡受体-1（programmeddeathreceptor-1，PD-1）和程序性死亡配体-1（programmeddeath-ligand1，PD-L1）。这些单克隆抗体具有重新激活针对

5、肿瘤细胞免疫系统的能力，但是也可能引起许多自身免疫副作用，称为免疫相关不良反应（immune-relatedadverseevents，irAEs）。irAEs可累及全身各个系统，且发生特点与传统化疗及靶向药物有很大差异。本文结合最新文献报道、指南，对抗CTLA-4单抗Ipilimumab、抗PD-1单抗Nivolumab和Pembrolizumab等药物在肺脏、肝脏、肾脏、胃肠道系统、内分泌系统、皮肤以及其他组织和器官的irAEs的发生率、可能发生机制、临床表现及治疗原则等方面进行综述。关键词：免疫

6、检查点抑制剂，免疫相关不良反应，细胞毒性T淋巴细胞相关抗原4，程序性死亡受体-1，程序性死亡配体-11英文摘要ToxicitiesandmanagementofimmunecheckpointinhibitorsincancerimmunotherapyABSTRACTInrecentyears,immunecheckpointinhibitors(ICPi)havebecomethestandardtreatmentformanyadvancedcancers.Themainlytargetsoft

7、hesedrugsincludecytotoxicTlymphocyte-associatedantigen4(CTLA-4),programmeddeathreceptor-1(PD-1)andprogrammeddeath-ligand1(PD-L1).Thesemonoclonalantibodieshavetheabilitytoreactivatetheimmunesystemofthetumorcells,butmayalsocausevariousautoimmunesideeffect

8、s,calledimmune-relatedadverseevents(irAEs).IrAEscanaffectalmostallorgansanditscharacteristicsaredifferentfromconventionalchemotherapyandtargetedtherapy.Accordingtotherecentlypublishedstudies,wewillreviewtheincidence，mechanism，cli