Department of Health Examination Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Pathology, The Friendship Hospital of Dalian, Dalian, China.
Front Immunol. 2024 Aug 13;15:1423775. doi: 10.3389/fimmu.2024.1423775. eCollection 2024.
Tertiary lymphoid structures (TLS), ordered structure of tumor-infiltrating immune cells in tumor immune microenvironment (TIME), play an important role in the development and anti-tumor immunity of various cancers, including liver, colon, and gastric cancers. Previous studies have demonstrated that the presence of TLS in intra-tumoral (IT), invasive margin (IM), and peri-tumoral (PT) regions of the tumors at various maturity statuses. However, the density of TLS in different regions of non-small cell lung cancer (NSCLC) has not been extensively studied.
TLS and tumor-infiltrating immune cells were assessed using immunohistochemistry (IHC) staining in 82 NSCLC patients. Tumor samples were divided into three subregions as IT, IM and PT regions, and TLS were identified as early/primary TLS (E-TLS) or secondary/follicular TLS (F-TLS). The distribution of TLS in different maturity statuses, along with their correlation with clinicopathological characteristics and prognostic value, was assessed. Nomograms were used to predict the probability of 1-, 3-, and 5-year overall survival (OS) in patients with NSCLC.
The density of TLS and proportion of F-TLS in the IT region (90.2%, 0.45/mm, and 61.0%, respectively) were significantly higher than those in the IM region (72.0%, 0.18/mm, and 39.0%, respectively) and PT region (67.1%, 0.16/mm, and 40.2%, respectively). A lower density of TLS, especially E-TLS in the IM region, was correlated with better prognosis in NSCLC patients. CD20+ B cells, CD3+ T cells, CD8+ cytotoxic T cells, and CD68+ macrophages were significantly overexpressed in the IM region. CD20+ B cells and CD3+ T cells in the IM region were significantly correlated with the density of E-TLS, while no statistically significant correlation was found with F-TLS. The E-TLS density in the IM region and TNM stage were independent prognostic factors for NSCLC patients. The nomogram showed good prognostic ability.
A higher density of E-TLS in the IM region was associated with a worse prognosis in NSCLC patients, potentially due to the inhibition of TLS maturation caused by the increased density of suppressive immune cells at the tumor invasion front.
三级淋巴结构（TLS）是肿瘤免疫微环境（TIME）中肿瘤浸润免疫细胞的有序结构，在包括肝癌、结肠癌和胃癌在内的各种癌症的发展和抗肿瘤免疫中发挥重要作用。先前的研究表明，TLS 存在于肿瘤内（IT）、侵袭边缘（IM）和肿瘤周围（PT）区域的各种成熟状态下。然而，非小细胞肺癌（NSCLC）不同区域 TLS 的密度尚未得到广泛研究。
在 82 名 NSCLC 患者中使用免疫组织化学（IHC）染色评估 TLS 和肿瘤浸润免疫细胞。肿瘤样本分为 IT、IM 和 PT 三个亚区，TLS 被鉴定为早期/原发性 TLS（E-TLS）或次级/滤泡性 TLS（F-TLS）。评估了 TLS 在不同成熟状态下的分布及其与临床病理特征和预后价值的相关性。使用列线图预测 NSCLC 患者 1、3 和 5 年总生存率（OS）的概率。
TLS 的密度和 IT 区域 F-TLS 的比例（分别为 90.2%、0.45/mm 和 61.0%）明显高于 IM 区域（分别为 72.0%、0.18/mm 和 39.0%）和 PT 区域（分别为 67.1%、0.16/mm 和 40.2%）。IM 区域 TLS 密度较低，尤其是 E-TLS，与 NSCLC 患者的预后较好相关。IM 区域中 CD20+B 细胞、CD3+T 细胞、CD8+细胞毒性 T 细胞和 CD68+巨噬细胞的表达明显上调。IM 区域的 CD20+B 细胞和 CD3+T 细胞与 E-TLS 的密度呈显著相关，而与 F-TLS 无统计学显著相关性。IM 区域 E-TLS 密度和 TNM 分期是非小细胞肺癌患者的独立预后因素。列线图显示了良好的预后能力。
IM 区域 E-TLS 密度较高与 NSCLC 患者预后较差相关，这可能是由于肿瘤侵袭前沿抑制性免疫细胞密度增加导致 TLS 成熟受阻所致。
