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多样化的遗传驱动免疫景观通过不同的机制决定肿瘤的进展。

Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms.

机构信息

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

出版信息

Nat Med. 2018 Feb;24(2):165-175. doi: 10.1038/nm.4463. Epub 2018 Jan 8.

Abstract

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.

摘要

多种免疫细胞类型可以浸润肿瘤,并通过不同的机制促进肿瘤的进展和转移,包括免疫抑制。目前尚不清楚肿瘤中不同的遗传改变如何影响免疫景观的组成。在这里,我们描述了由关键肿瘤抑制基因 Pten 缺失驱动的前列腺癌的免疫细胞组成,无论是单独缺失还是与 Trp53、Zbtb7a 或 Pml 的缺失联合缺失。我们观察到一种显著的定量和定性异质性,这种异质性直接取决于肿瘤中的特定遗传事件,从“冷”、非炎症肿瘤到大量浸润的景观——这是具有重要治疗意义的结果。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,基于整合的基因型-免疫表型分析对患者进行分层,可能是成功进行临床试验和定制精确免疫治疗的必要条件。

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