JAMA:三阴性乳腺癌免疫浸润与何相关?

2017-08-08 xuyihan MedSci原创

为什么有些三阴性乳腺癌(TNBCs)有高而其他有低的免疫细胞浸润呢?关于这一点目前知之甚少。了解免疫监视如何塑造癌症基因可能有助于区分病人和制定更有效的免疫治疗策略。为了检测TNBCs中基因组中度量与免疫浸润程度的关系,Thomas Karn等人进行了相关研究。

为什么有些三阴性乳腺癌(TNBCs)有高而其他有低的免疫细胞浸润呢?关于这一点目前知之甚少。了解免疫监视如何塑造癌症基因可能有助于区分病人和制定更有效的免疫治疗策略。为了检测TNBCs中基因组中度量与免疫浸润程度的关系,Thomas Karn等人进行了相关研究。

该研究自2015年6月1日起至2017年1月31日,利用DNA和RNA测序数据以及从癌症基因组阿特拉斯(TCGA)乳腺癌数据集(n=1215)获得的信使RNA表达结果,来计算先前描述的免疫宏基因表达值和组织淋巴细胞计数,从而定量免疫浸润和对TNBCs的预后分类。它使用了乳腺癌国际协会分子分类(METABRIC)的数据子集作为一个独立的验证队列。研究比较了免疫丰富预后好的TNBCs队列与免疫差预后差的TNBCs队列之间的克隆异质性、躯体总突变负荷、新抗原负载以及躯体细胞拷贝数变化水平。本研究还比较了在119个典型癌基因中的突变分布。

该研究纳入的有生存资料的193例TNBC患者,发现克隆异质性与免疫宏基因表达呈负相关(ρ=-0.395,P = 2×10-8)。研究还发现免疫宏基因表达与体细胞拷贝数变化水平之间呈负相关(ρ=-0.484,P = 2×10-10)。淋巴细胞富集且预后好的TNBCs较淋巴细胞少且预后差的TNBCs有显着较低的变异和新抗原计数。这项研究的结果通过在同一TCGA数据子集和独立METABRIC数据子集使用各种免疫宏基因得到了强有力的佐证。

这项研究表明,免疫丰富TNBCs可能是一种免疫监视,不断消除了许多免疫克隆,从而导致较低的克隆异质性。这些癌症也可能代表TNBCs的一个子集,可能从免疫检查点抑制剂治疗从而获得免疫系统平衡中获益。

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    2017-08-10 luominglian113

    学习了,谢谢分享

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    2017-08-10 xlysu
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