脑转移
免疫系统
转移
医学
腺癌
外显子组测序
肺癌
基因组不稳定性
癌症
免疫疗法
癌症研究
突变
免疫学
生物
基因
肿瘤科
内科学
遗传学
DNA
DNA损伤
作者
Xin Wang,Hua Bai,Jiyang Zhang,Zhijie Wang,Jianchun Duan,Hong‐Qing Cai,Zheng Chen,Lin Q,Xiaobo Ding,Yiting Sun,Wei Zhang,Xiang Xu,Chunyan Hao,Dadong Zhang,Xiaoli Feng,Jinghai Wan,Jiexin Zhang,Jie Wang,Jing He
标识
DOI:10.1016/j.jtho.2023.09.276
摘要
IntroductionBrain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown.MethodsWhole-exome sequencing and RNA sequencing were performed on 30 matched brain metastasis, primary lung adenocarcinoma, and normal tissues. Data from The Cancer Genome Atlas primary lung adenocarcinoma cohort, including multiplex immunofluorescence, were used to support the findings of bioinformatics analysis.ResultsOur study highlights the key role of intratumor heterogeneity of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency or other somatic copy number alteration–associated mutation mechanisms, leading to increased genomic instability and genomic complexity. We further proposed a selection model of brain metastatic evolution in which intratumor heterogeneity drives immune remodeling, leading to immune escape through different mechanisms under local immune pressure.ConclusionsOur findings provide novel insights into the metastatic process and immune escape mechanisms of brain metastasis and pave the way for precise immunotherapeutic strategies for patients with lung cancer with brain metastasis.
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