Brain 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.Whole-exome sequencing and RNA-sequencing was performed on 30 matched brain metastasis (BM), primary lung adenocarcinoma (LP) and normal tissues. Data from TCGA primary lung adenocarcinoma (LUAD) cohort, as well as multiplex immunofluorescence (mIF), was used to support the findings of bioinformatics analysis.Our study highlights the key role of intratumour heterogeneity (ITH) of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency (HRD) or other somatic copy number alteration (SCNA)-associated mutation mechanisms, leading to increased genomic instability and genomic complexity. We further proposed a selection model of brain metastatic evolution in which ITH drives immune remodelling, leading to immune escape through different mechanisms under local immune pressure.Our findings provide novel insights into the metastatic process and immune escape mechanisms of brain metastasis and pave the way for precise immunotherapeutic strategies for lung cancer patients with brain metastasis.Copyright © 2023. Published by Elsevier Inc.