Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromso, Norway.
Department of Medical Biology, UiT, The Arctic University of Norway, Tromso, Norway.
Br J Cancer. 2021 May;124(10):1680-1689. doi: 10.1038/s41416-021-01307-y. Epub 2021 Mar 15.
We previously proposed an immune cell score (tumour node metastasis (TNM)-Immune cell score) classifier as an add-on to the existing TNM staging system for non-small cell lung cancer (NSCLC). Herein, we examined how to reliably assess a tertiary lymphoid structure (TLS) score to refine the TNM staging system.
Using immunohistochemistry (CD8/cytokeratin), we quantified TLS in resected NSCLC whole-tumour tissue sections with three different scoring models on two independent collections (total of 553 patients). In a pilot setting, NanoString gene expression signatures were analysed for associations with TLS.
The number of TLSs significantly decreased in stage III patients as compared to stage II. The TLS score was an independent positive prognostic factor, regardless of the type of (semi)-quantification strategy used (four-scale semi-quantitative; absolute count of total TLS; subpopulation of mature TLS) or the endpoint (disease-specific survival; overall survival; time to recurrence). Subgroup analyses revealed a significant prognostic impact of TLS score within each pathological stage, patient cohort and main histological subtype. Targeted gene expression analysis showed that high TLS levels were associated with the expression of B cell and adaptive immunity genes/metagenes including tumour inflammation signature.
The TLS score increases the prognostic power in each pathological stage and hence has the potential to refine TNM staging in resected NSCLC.
我们之前提出了一种免疫细胞评分（肿瘤淋巴结转移（TNM）-免疫细胞评分）分类器，作为非小细胞肺癌（NSCLC）现有 TNM 分期系统的补充。在此，我们研究了如何可靠地评估三级淋巴结构（TLS）评分，以完善 TNM 分期系统。
我们使用免疫组织化学（CD8/细胞角蛋白），在两个独立的数据集（共 553 例患者）的 NSCLC 全肿瘤组织切片上，使用三种不同的评分模型来量化 TLS。在一个初步研究中，我们分析了 NanoString 基因表达谱与 TLS 的相关性。
与 II 期患者相比，III 期患者的 TLS 数量明显减少。TLS 评分是一个独立的阳性预后因素，无论使用哪种（半）定量策略（四级半定量；总 TLS 计数；成熟 TLS 亚群）或终点（疾病特异性生存；总生存；复发时间）。亚组分析显示，TLS 评分在每个病理分期、患者队列和主要组织学亚型中均具有显著的预后影响。靶向基因表达分析表明，TLS 水平较高与 B 细胞和适应性免疫基因/元的表达相关，包括肿瘤炎症特征。
TLS 评分增加了每个病理分期的预后能力，因此有可能改善 NSCLC 的 TNM 分期。
