Background:Biliary tract cancers(BTCs)comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses.The benefit of chemotherapy seems to have reached a bottleneck and,therefore,new effective therapeutic strategies for advanced BTCs are needed.Molecularly targeted therapies in se-lected patients are rapidly changing the situation.However,the low frequency of specific driver alter-ations in BTCs limits their wide application.Recently,immunotherapeutic approaches are also under ac-tive investigation in BTCs,but the role of immunotherapy in BTCs remains controversial.Data sources:PubMed,Web of Science,and meeting resources were searched for relevant articles pub-lished from January 2017 to May 2022.The search aimed to identify current and emerging immunothera-peutic approaches for BTCs.Information on clinical trials was obtained from in BTC patients is currently under investigation,and most of the investigations focused on the application of immune checkpoint inhibitors(ICIs).However,only a subgroup of BTCs with microsatellite-instability high(MSI-H)/DNA mismatch repair-deficient(dMMR)or tumor mutational burden-high(TMB-H)benefit from monotherapy of ICIs,and limited activity was observed in the second or subsequent settings.Nevertheless,promising results come from studies of ICIs in combination with other therapeutic approaches,including chemotherapy,in advanced BTCs,with a moderate toxicity pro-file.Recent studies demonstrated that compared to GEMCIS alone,durvalumab plus GEMCIS significantly improved patient survival(TOPAZ-1 trial)and that ICIs-combined chemoimmunotherapy is poised to be-come a new frontline therapy option,regardless of TMB and MMR/MSI status.Adoptive cell therapy and peptide-or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs.Numerous biomarkers have been investigated to define their predictive role in response to ICIs,but no predictive biomarker has been validated,except MSI-H/dMMR.Conclusions:The role of immunotherapy in BTCs is currently under investigation and the results of on-going studies are eagerly anticipated.Several studies have demonstrated the safety and efficacy of ICIs in combination with chemotherapy in treatment-naive patients,such as the phase Ⅲ TOPAZ-1 trial,which will change the standard care of first-line chemotherapy for advanced BTCs.However,further research is needed to understand the best combination with immunotherapy and to discover more predictive biomarkers to guide clinical practice.

Zhen-Gang Yuan;Tian-Mei Zeng;Chen-Jie Tao

Department of Oncology,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University(Navy Medical University),Shanghai 200438,China

国际肝胆胰疾病杂志(英文版)

[1]Zhen-Gang Yuan;Tian-Mei Zeng;Chen-Jie Tao-.Current and emerging immunotherapeutic approaches for biliary tract cancers)[J].国际肝胆胰疾病杂志(英文版),2022(05):440-449

BTCs,immunothera,GEMCIS,chemoimmunotherapy,Adoptive

Current,emerging,immunotherapeutic,approaches,biliary,tract,cancers,Background,Biliary,comprise,heterogeneous,aggressive,malignancies,unfavorable,prognoses,benefit,chemotherapy,seems,have,reached,bottleneck,therefore,new,effective,strategies,advanced,needed,Molecularly,targeted,therapies,lected,patients,rapidly,changing,situation,However,low,frequency,specific,driver,alter,limits,their,wide,application,Recently,also,but,role,remains,controversial,Data,meeting,resources,were,searched,relevant,articles,pub,lished,from,January,May,aimed,identify,Information,clinical,trials,was,obtained,currently,most,investigations,focused,immune,checkpoint,inhibitors,ICIs,only,subgroup,microsatellite,instability,high,MSI,mismatch,repair,deficient,dMMR,tumor,mutational,burden,TMB,monotherapy,limited,activity,observed,second,subsequent,settings,Nevertheless,promising,results,come,studies,combination,including,moderate,toxicity,file,demonstrated,that,compared,alone,durvalumab,plus,significantly,improved,survival,TOPAZ,combined,poised,frontline,regardless,status,cell,peptide,dendritic,vaccines,options,being,studied,Numerous,biomarkers,been,investigated,define,predictive,response,validated,except,Conclusions,going,eagerly,anticipated,Several,safety,efficacy,treatment,naive,such,phase,which,will,change,standard,care,first,further,research,understand,best,discover,more,guide,practice

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