Hypermutated tumours across 11 cancer types show three distinct immune subtypes
Hypermutated tumours across 11 cancer types show three distinct immune subtypes
复制标题
11 种癌症类型的超突变肿瘤显示出三种不同的免疫亚型
DOI：
10.1016/j.ejca.2021.01.044
复制
发表时间：
2021-03-19
影响因子：
8.4
通讯作者：
Yang, Yanmei
中科院分区：
文献类型：
--
作者：
Hu, Wangxiong;Chen, Jiani;Yang, Yanmei
背景：免疫检查点阻断疗法后，不到一半的高突变（HM）肿瘤能实现完全缓解，这表明HM肿瘤具有高度异质性。因此，迫切需要解析未知的内在HM肿瘤亚型。
方法：对来自癌症基因组图谱（The Cancer Genome Atlas）的11种癌症类型的5519个肿瘤以及来自一个亚洲队列的338个结直肠癌（CRC）样本的体细胞突变数据进行统计分析。肿瘤突变负荷＞10个突变/兆碱基的样本被归类为HM。共有1040个具有相应转录组的HM样本用于非负矩阵分解聚类。比较各亚型之间的肿瘤突变负荷、新抗原、T细胞受体（TCR）多样性、基质评分和免疫评分。
结果：HM肿瘤可分为三种不同的免疫亚型：HM1、HM2和HM3。HM3肿瘤与CD8 T细胞浸润增加、TCR多样性高、免疫评分高以及生存期延长相关。HM2肿瘤与丰富的基质成分、上皮 - 间充质转化、转化生长因子β（TGF-β）、血管生成特征以及不良预后相关。通过免疫荧光在结直肠癌中验证了HM3中更多CD8 T细胞的浸润和趋化因子表达的增加。
结论：这些发现将有助于在不久的将来制定以亚型为导向的治疗策略，以提高治疗效果。（C）2021爱思唯尔有限公司。保留所有权利。
Background: Complete remission is observed in less than half of hypermutated (HM) tumours after immune checkpoint blockade therapy, indicating that HM tumours are very heterogeneous. Thus, there is an urgent requirement to decipher the unknown intrinsic HM tumour subtypes.Methods: Statistical analysis was performed on somatic mutation data from 5519 tumours across 11 cancer types obtained from The Cancer Genome Atlas and 338 colorectal cancer (CRC) samples obtained from an Asian cohort. Samples with a tumour mutation burden >10 mut/Mb were classified as HM. A total of 1040 HM samples harbouring corresponding transcriptomes were used for non-negative matrix factorisation clustering. Tumour mutational burden, neoantigens, T cell receptor (TCR) diversity, stromal score and immune score were compared between the subtypes.Results: HM tumours fell into three distinct immune subtypes: HM1, HM2 and HM3. HM3 tumours were correlated with increased CD8 T cell infiltration, high TCR diversity, a high immune score and prolonged survival. HM2 tumours were correlated with an abundant stromal component, epithelialemesenchymal transition, TGF beta, angiogenesis hallmarks and poor outcomes. The infiltration of more CD8 T cells and increased chemokine expression in HM3 were validated in CRC by immunofluorescence.Conclusions: These findings will facilitate the development of a subtype-oriented therapy strategy to enhance the treatment effect in the near future. (C) 2021 Elsevier Ltd. All rights reserved.