Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms
Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms
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DOI：
10.1038/nm.4463
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发表时间：
2018-02-01
期刊：
影响因子：
82.9
通讯作者：
Pandolfi, Pier Paolo
中科院分区：
文献类型：
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作者：
Bezzi, Marco;Seitzer, Nina;Pandolfi, Pier Paolo
多种免疫细胞类型可以浸润肿瘤，并通过不同的机制（包括免疫抑制）促进肿瘤进展和转移。目前尚不清楚肿瘤中不同的基因改变如何影响免疫景观的组成。在这里，我们表征了由关键肿瘤抑制基因 Pten 的缺失（单独或与 Trp53、Zbtb7a 或 Pml 的缺失相结合）驱动的前列腺癌的免疫细胞组成。我们观察到了惊人的定量和定性异质性，该异质性直接取决于肿瘤中的特定遗传事件，范围从“冷”、非发炎肿瘤到大规模浸润的景观，这些结果具有重要的治疗意义。此外，我们在人类前列腺癌样本的转录组分析中显示了这些定性差异。这些数据表明，基于综合基因型-免疫表型分析的患者分层对于成功的临床试验和定制的精准免疫治疗可能是必要的。
Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes-results with important therapeutic implications. Further, we showed these qualitative differences in transcriptomic analysis of human prostate cancer samples. These data suggest that patient stratification on the basis of integrated genotypic-immunophenotypic analyses may be necessary for successful clinical trials and tailored precision immunological therapies.