Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.
三级淋巴结构（TLSs）是在非淋巴组织中因炎症或癌症而形成的复杂淋巴细胞簇。具有增殖性生发中心的成熟TLS与多种癌症的良好预后相关。然而，TLS成熟度对晚期结直肠癌（CRC）的影响尚未明确。本研究分析了78例病理分期为T4的CRC患者手术切除肿瘤中TLS成熟度及肿瘤Ki-67表达的意义。成熟TLS被定义为具有Ki-67阳性增殖生发中心的T细胞和B细胞有序浸润。我们分析了TLS成熟度与肿瘤内免疫细胞浸润的关系。具有生发中心Ki-67表达的成熟TLS与微卫星不稳定性及生存改善相关；但在同一队列中，高肿瘤Ki-67表达与不良生存相关。多变量分析确定，缺乏成熟TLS是复发后总生存不良的独立预测因子。与缺乏成熟TLS的肿瘤相比，具有成熟TLS的肿瘤中T淋巴细胞和巨噬细胞的瘤内浸润显著增加。高Ki-67水平和缺乏成熟TLS被确定为晚期CRC的不良预后因素。成熟TLS可作为高风险CRC患者的一个有前景的标志物。
肿瘤(癌症)患者之家