小柯机器人

研究使用DNA测序数据来量化T细胞分数和治疗反应
2021-09-12 12:54

英国伦敦大学学院Nicholas McGranahan团队使用DNA测序数据来量化T细胞分数和治疗反应。2021年9月8日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示,免疫微环境影响着肿瘤的演化,既可以预测预后,又可以预测对免疫疗法的反应。然而,对肿瘤浸润淋巴细胞(TIL)的测量由于缺乏适当的数据而受到限制。DNA全外显子组测序(WES)经常被用来计算肿瘤的突变负担和鉴别可靶向的突变。

为此,研究人员开发了T细胞外显子TREC工具(T cell ExTRECT),这是一种利用T细胞受体-α基因(TCRA,也称为TRA)的V(D)J重组过程中T细胞受体切除圈(TREC)丢失的信号来估计WES样本中T细胞比例的方法。TCRA T细胞分数与正交TIL估计值相关,与样本类型无关。女性的血液TCRA T细胞分数高于男性,并与肿瘤免疫浸润和细菌测序读数的存在相关。肿瘤TCRA T细胞分数在肺腺癌中具有预后作用。

通过对接受免疫治疗的肿瘤进行荟萃分析,研究人员发现肿瘤TCRA T细胞分数可以预测免疫治疗的反应,并提供了测量肿瘤突变负担以外的价值。将T细胞ExTRECT应用于一个多样本的泛癌症队列,结果显示出肿瘤内免疫浸润程度的高度多样性。包含SPPL3的12q24.31-32亚克隆缺失与TCRA T细胞分数的减少有关。T细胞ExTRECT提供了一种成本效益高的技术来描述免疫浸润和体细胞变化的特征。

附:英文原文

Title: Using DNA sequencing data to quantify T cell fraction and therapy response

Author: Bentham, Robert, Litchfield, Kevin, Watkins, Thomas B. K., Lim, Emilia L., Rosenthal, Rachel, Martnez-Ruiz, Carlos, Hiley, Crispin T., Bakir, Maise Al, Salgado, Roberto, Moore, David A., Jamal-Hanjani, Mariam, Swanton, Charles, McGranahan, Nicholas

Issue&Volume: 2021-09-08

Abstract: The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-α gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31–32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes.

DOI: 10.1038/s41586-021-03894-5

Source: https://www.nature.com/articles/s41586-021-03894-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0