The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
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DOI：
10.1016/j.celrep.2019.04.098
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发表时间：
2019-05-28
期刊：
影响因子：
8.8
通讯作者：
Caldas, Carlos
中科院分区：
文献类型：
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作者：
De Mattos-Arruda, Leticia;Sammut, Stephen-John;Caldas, Carlos
致死性癌症的详细分子表征是了解对治疗的抗性和逃避癌症免疫编辑的先决条件。我们对10例耐药乳腺癌患者尸检中的多区域转移进行了广泛的多平台分析。整合的基因组和免疫景观显示，转移瘤作为克隆群落传播和进化，揭示了它们预测的新抗原景观，并显示它们可以积累HLA杂合性丢失（洛）。这些数据进一步确定了可变的肿瘤微环境，并通过对T细胞受体库的分析揭示了适应性免疫反应似乎与转移性基因组共同进化。这些发现揭示了致命的转移性乳腺癌的细节。
The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.