Department of General surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.
Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Cancer Med. 2023 Feb;12(3):3068-3078. doi: 10.1002/cam4.5227. Epub 2022 Sep 9.
The positive prediction of prognosis and immunotherapy within tertiary lymphoid structure (TLS) in cancerous tissue has been well demonstrated, including liver cancer. However, the relationship between TLS and prognosis in the peritumoral region of hepatocellular carcinoma (HCC) has received less attention. Few studies on whether TLS, as a typical representative of acquired immune cell groups, is associated with innate immune cells. The aim of this paper was to identify the prognostic role of peritumor TLS in HCC and to simply explore the relationship with neutrophils infiltration.
This study included cancerous and paracancerous tissue from 170 patients after surgical resection of HCC. TLS was examined and identified by pathological H&E examination, and the impact on prognosis was further classified by determination of total TLS area. Immunohistochemical staining of CD15+ neutrophils was also performed on half of the cases. The obtained results were validated by external public database, as TLS has been widely shown to be tagged with 12 chemokines.
In peritumoral tissue, the TLS- group had better overall survival (OS) and disease-free survival (DFS) outcomes compared with the TLS+ group. On the contrary, the intratumor TLS+ group showed better DFS outcomes. When further investigating the relationship between TLS area distribution and DFS, progressively worse prognosis was only found in the peritumor region with increasing TLS density (TLS- vs. TLS vs. TLS ). In addition, neutrophil infiltration increased in parallel with TLS density in the peritumoral region, which was not observed in the intratumoral region.
TLS might have a dual prognostic role in different regions of HCC. The abundance of peritumoral TLS is an independent influence of DFS. The inconsistent correlation between neutrophils and corresponding TLS in different regions may indicate different pathways of immune aggregation and may serve as an explanation for the different prognosis of TLS, which needs to be specifically explored.
在癌症组织中，三级淋巴结构（TLS）对预后和免疫治疗的积极预测已经得到了很好的证明，包括肝癌。然而，TLS 与肝癌肿瘤周围区域的预后之间的关系受到的关注较少。关于 TLS 是否作为获得性免疫细胞群的典型代表与固有免疫细胞相关的研究较少。本文旨在确定肝癌肿瘤周围 TLS 的预后作用，并简单探讨其与中性粒细胞浸润的关系。
本研究纳入了 170 例肝癌患者手术后的癌旁和癌组织。通过病理 H&E 检查观察和识别 TLS，并通过测定总 TLS 面积进一步对预后进行分类。对一半病例进行 CD15+中性粒细胞的免疫组织化学染色。通过外部公共数据库验证了研究结果，因为已经广泛证明 TLS 与 12 种趋化因子有关。
在肿瘤周围组织中，与 TLS+组相比，TLS-组的总生存（OS）和无病生存（DFS）结果更好。相反，肿瘤内 TLS+组的 DFS 结果更好。当进一步研究 TLS 区域分布与 DFS 的关系时，仅在肿瘤周围区域 TLS 密度增加（TLS-<TLS< TLS ）时发现预后逐渐恶化。此外，肿瘤周围区域的中性粒细胞浸润与 TLS 密度平行增加，而在肿瘤内区域则没有观察到这种情况。
TLS 在 HCC 的不同区域可能具有双重预后作用。肿瘤周围 TLS 的丰度是 DFS 的独立影响因素。不同区域中性粒细胞与相应 TLS 之间的不一致相关性可能表明免疫聚集的不同途径，并可能解释 TLS 不同的预后，这需要进一步研究。
