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Favorable response to immunotherapy in a pancreatic neuroendocrine tumor with temozolomide-induced high tumor mutational burden

查看全文 作　　者：Yanshuo [1]Cao;Yutong [2]Ma;Jiangyuan [3]Yu;Yu [4]Sun;Tingting [5]Sun;Yang [5,6]Shao;Jie [1]Li;Lin [1,7]Shen;Ming [1]Lu 高影响力作者 机构地区：[1]Department of Gastrointestinal Oncology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Peking University Cancer Hospital&Institute,Beijing 100142,P.R.China;[2]Translational Medicine Research Institute,Geneseeq Technology Inc.,Toronto M5T1K5,Canada;[3]Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Beijing 100142,P.R.China;[4]Department of Pathology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Peking University Cancer Hospital&Institute,Beijing 100142,P.R.China;[5]Nanjing Geneseeq Technology Inc.,Nanjing,Jiangsu 210032,P.R.China;[6]School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 210029,P.R.China;[7]Department of Early Drug Development Center,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Beijing 100142,P.R.China高影响力机构 出　　处：《Cancer Communications》索引2020年第40卷第12期,共6页高影响力期刊 摘　　要：Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options.Among such tumors,treatment for pancreatic neuroendocrine tumor(PanNET)G3 is the most difficult.Temozolomide(TMZ)is commonly used to treat PanNET.However,TMZ may cause tumor gene alkylation,which induces drug resistance and rapid disease progression.Herein,we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab,an anti-programmed cell death-ligand 1(anti-PD-L1)monoclonal antibody,after multiple cycles of TMZ treatment.Genomic profiling revealed that compared with the patient’s samples collected at baseline,the postTMZ-treatment samples had markedly higher levels of tumor mutational burden(TMB)associated with characteristic alkylating mutational signature representing a positive correlation with favorable response to anti-PD-1 treatment.In addition,we observed a germline truncating mutation of MUTYH(W156*)that was considered to be pathogenic and potentially conferred to genomic instability.This case suggests that anti-PD-1 therapy could be a treatment option for PanNET patients with increased TMB after TMZ-based treatment. 关 键 词：gene expression profiling mutational signature neuroendocrine tumors programmed cell death 1 receptor TEMOZOLOMIDE tumor mutational burden
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