Zhang Nana, Zhang Guanjun, Wang Depu, Liu Hao, Zhang Yuchi, Ayarick Vivian Adiila, Han Xuan, Lv Yi, Wang Yili
Center for Regenerative and Reconstructive Medicine, Med-X Institute of Western China Science and Technology Innovation Harbour, The First Affiliated Hospital of Xian JiaoTong University, China.
National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, China.
Arch Med Sci. 2021 Aug 2;20(1):255-266. doi: 10.5114/aoms/140622. eCollection 2024.
To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC).
The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40.
The TLS distribution was significantly higher in the tumor invasive edge than the tumor center ( < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs ( = 0.007), peri-CD8+ ( = 0.019) and peri-GrB+TILs ( = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs ( = 0.019) and TLSs ( = 0.037) were independent prognostic predictor for GC patients.
We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.
探讨三级淋巴结构（TLSs）与肿瘤浸润淋巴细胞（TILs）之间的关系、它们的分布特征以及在胃癌（GC）中的预后价值。
通过免疫组织化学（IHC）染色评估TLSs和TILs的四种亚型。在GC组织异位淋巴细胞聚集区域中鉴定出的MECA-79阳性高内皮静脉（HEV）的存在被定义为有效的TLSs。在肿瘤中心、浸润边缘和TLSs内最阳性细胞的5个视野中观察标记的TILs数量，视野为×40。
TLSs在肿瘤浸润边缘的分布明显高于肿瘤中心（<0.001）。同样，肿瘤浸润边缘的CD8 + T细胞和GrB + T细胞浸润密度在统计学上显著高于肿瘤中心。TILs总数和FOXP3 + T细胞呈现相反的分布。TLSs和TILs的密度与位置和免疫表型均呈正相关。较高频率的TILs和TLSs通常与良好的临床病理参数相关。较高数量的TLSs周围（= 0.007）、CD8 +周围（= 0.019）和GrB + TILs周围（= 0.032）与良好的总生存期显著相关。多变量分析显示，TILs（= 0.019）和TLSs（= 0.037）的密度是GC患者的独立预后预测指标。
我们提供的证据表明，TLSs与GC中的淋巴细胞浸润呈正相关。因此，TLSs的形成预示着有利的免疫系统功能，可被视为一种新的生物标志物，用于分层未治疗GC患者的总生存风险。
