检查点抑制剂诱导的毒性作用与非小细胞肺癌

SCI

1May

AssociationofCheckpointInhibitor–InducedToxicEffectsWithSharedCancerandTissueAntigensinNon–SmallCellLungCancer

BernerF,BomzeD,DiemS,etal.AssociationofCheckpointInhibitor-InducedToxicEffectsWithSharedCancerandTissueAntigensinNon-SmallCellLungCancer.JAMAOncol.

CorrespondingAuthor:LukasFlatz,MD,DepartmentofDermatologyandAllergology,KantonsspitalStGallen,RorschacherStrasse95,StGallen,Switzerland(Lukas.Flatz

IMPORTANCE重要性

ImmunotherapywithcheckpointinhibitorstargetingthePD-1(programmedcelldeath1)axishasbroughtnotableprogressinpatientswithnon–smallcelllungcancer(NSCLC)andothercancers.However,autoimmunetoxiceffectsarefrequentandpoorlyunderstood,makingitimportanttounderstandthepathophysiologicprocessesofautoimmuneadverseeffectsinducedbycheckpointinhibitortherapy.

针对PD-1（程序性细胞死亡1）轴的检查点抑制剂免疫治疗在非小细胞肺癌（NSCLC）和其他癌症患者中取得了显著进展。然而，自身免疫性毒性效应频繁发生且对此知之甚少；因此，了解检查点抑制剂治疗诱导的自身免疫不良反应的病理生理过程非常重要。

OBJECTIVE目标

Togainmechanisticinsightintoautoimmuneskintoxiceffectsinducedbyanti–PD-1treatmentinpatientswithnon–smallcelllungcancer.

了解抗-PD-1治疗对非小细胞肺癌患者自身免疫性皮肤毒性的机制。

DESIGN,SETTING,ANDPARTICIPANTS设计，设置与参与者

ThisprospectivecohortstudywasconductedfromJuly1,,toDecember31,.Patients(n=73)withnonsmallcelllungcancerwhoreceivedanti–PD-1therapy(nivolumaborpembrolizumab)wererecruitedfrom4differentcentersinSwitzerland(KantonsspitalStGallen,SpitalGrabs,SpitalWil,andSpitalFlawil).Peripheralbloodmononuclearcells,tumorbiopsyspecimensandbiopsiesfromsitesofautoimmuneskintoxiceffectswerecollectedovera2-yearperiod,withpatientfollow-upafter1year.

本前瞻性队列研究于年7月1日至年12月31日进行。非小细胞肺癌患者（n=73）接受抗PD-1治疗（nivolumab或pembrolizumab），从瑞士的4个不同中心（KantonsspitalStGallen、SpitalGrabs、SpitalWil和SpitalDefectil）招募。在2年内收集外周血单核细胞，肿瘤活检标本和来自自身免疫性皮肤毒性作用部位的活组织检查，患者随访1年。

MAINOUTCOMESANDMEASURES主要结果与方法

Responsetotreatment,overallsurvival,progression-freesurvival,anddevelopmentofautoimmunetoxiceffects(basedonstandardlaboratoryvaluesandclinicalexaminations).

治疗响应、总生存率、无进展生存率和自身免疫毒性效应的发展（基于标准实验室值和临床检查）。

RESULTS结果

Ofthecohortof73patientswithNSCLC(mean[SD]age,68.1[8.9]years;44[60%]men),25(34.2%[95%CI,24.4%-45.7%])developedautoimmuneskintoxiceffects.Ofthe73patientswithNSCLC,25(34.2%[95%CI,24.4%-45.7%])developedautoimmuneskintoxiceffects,whichweremorefrequentinpatientswith