关键词: immune cell infiltration locally advanced colorectal cancer tertiary lymphoid structures

来  源:   DOI:10.3390/cancers16152684   PDF(Pubmed)

Abstract:
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.
摘要:
三级淋巴结构(TLSs)是由于炎症或癌症而在非淋巴组织中出现的复杂淋巴细胞簇。具有增殖生发中心的成熟TLS与各种癌症的良好预后相关。然而,TLS成熟度对晚期结直肠癌(CRC)的影响尚待研究.我们分析了78例病理T4CRC患者手术切除的肿瘤中TLS成熟度和肿瘤Ki-67表达的意义。成熟TLS定义为具有Ki-67阳性增殖生发中心的T和B细胞的有组织浸润。我们分析了TLS成熟度与肿瘤内免疫细胞浸润之间的关系。成熟TLS伴生发中心Ki-67表达与微卫星不稳定性和生存率改善有关;在同一队列中,高肿瘤Ki-67表达与低生存率相关.多变量分析确定缺乏成熟的TLS是复发后总生存率差的独立预测因子。与缺乏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着升高。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。成熟的TLS可以作为CRC高风险患者的有希望的标志物。
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