Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma
Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma
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三级淋巴结构和肿瘤浸润淋巴细胞在口腔鳞癌中的预后价值
DOI：
10.1038/s41368-020-00092-3
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发表时间：
2020-09-15
影响因子：
14.9
通讯作者：
Wang, Zhi
中科院分区：
文献类型：
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作者：
Li, Qunxing;Liu, Xiangqi;Wang, Zhi
三级淋巴样结构（TLS）是癌症中的异位淋巴样结构，在很大程度上与良好的预后有关。然而，TLSs在口腔鳞状细胞癌（OSCC）中的预后价值在很大程度上是未知的，肿瘤浸润淋巴细胞（til）和TLSs之间的关系在OSCC中很少被探讨。在这项研究中，我们检测了168例OSCC患者的TLS相关标志物，包括高内皮小静脉的外周节点地址（PNAd）、B细胞中的CD20和T细胞中的CD3，并在TLS阳性和TLS阴性队列之间进行了生存分析。我们通过染色CD8+细胞毒性T细胞和CD57+ NK细胞来检测TILs的存在。45例（26.8%）TLSs表现为高度组织化结构。tls阳性患者的5年总生存率（OS）（88.9%比56.1%，P< 0.001）和无复发生存率（RFS）（88.9%比63.4%，P= 0.002）更高。此外，在多因素分析中，TLS的存在是5年OS率（风险比[HR] = 3.784, 95%可信区间[CI]， 1.498-9.562）和RFS率（HR = 3.296, 95% CI, 1.279-8.490）的独立预后因素。此外，在tls阳性切片中发现CD8+ T细胞和CD57+ NK细胞的密度高于tls阴性切片（P< 0.001），它们的组合提供了更高的预测精度（AUC = 0.730; 95% CI, 0.654-0.805）。总之，我们的研究结果表明TLS是OSCC患者预后的独立阳性因素。这些发现为今后TLSs在OSCC治疗中的诊断和治疗价值提供了理论基础。
Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%,P< 0.001) and relapse-free survival (RFS) rate (88.9% vs. 63.4%,P= 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498–9.562) and RFS rate (HR = 3.296; 95% CI, 1.279–8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P< 0.001), and their combination provided a higher predictive accuracy (AUC = 0.730; 95% CI, 0.654–0.805). In conclusion, our results suggest that TLS is an independent positive prognostic factor for OSCC patients. These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.