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Existence of intratumoral tertiary lymphoid structures is associated with immune cells infiltration and predicts better prognosis in early-stage hepatocellular carcinoma.

肿瘤内三级淋巴结构的存在与免疫细胞浸润相关,预示早期肝细胞癌预后较好。

  • 影响因子:5.5150
  • DOI:10.18632/aging.102821
  • 作者列表:"Li H","Wang J","Liu H","Lan T","Xu L","Wang G","Yuan K","Wu H
  • 发表时间:2020-02-22
Abstract

:Tumor-associated tertiary lymphoid structures (TLS) play a critical role in the progression of various tumors. However, the dynamics of lymphocyte recruitment during hepatocellular carcinoma (HCC) clinical progression have not been fully elucidated. In the present study, tissue microarrays and hematoxylin-eosin staining were used to evaluate the existence and degree of TLS in HCC patients. Nine immune biomarkers in intratumoral tissues were examined by immunohistochemical staining. A total of 462 patients were recruited for the study. Kaplan-Meier analysis showed that TLS was inversely correlated with the risk of early tumor recurrence (P=0.014), whereas no association was found between TLS and overall survival. Cox regression analysis identified TLS as an independent prognostic factor for early HCC recurrence (P=0.005). In addition, TLS was associated with increased intratumoral CD3+, CD8+, CD20+, and decreased infiltration of Foxp3+ and CD68+ cells. A lower density of PD1+, TIM3+, and LAG3+ were found in TLS+ cases. Sub-analysis revealed the prognostic value of TLS on early-stage HCC (BCLC 0-A, TNM stage I-II) and HCC with solitary nodule. The validation cohort verified the prognostic value of TLS in early-stage HCC patients. These results suggest that TLS-targeted immune-modulating therapies may be a potential strategy for effective immune-mediated tumor suppression.

摘要

: 肿瘤相关三级淋巴结构 (TLS) 在多种肿瘤的进展中起关键作用。然而,肝细胞癌 (HCC) 临床进展过程中淋巴细胞募集的动力学尚未完全阐明。在本研究中,组织微阵列和苏木精-伊红染色用于评估 HCC 患者中 TLS 的存在和程度。免疫组织化学染色检测了 9 种瘤内组织中的免疫生物标志物。共招募了 462 例患者进行研究。Kaplan-Meier 分析显示,TLS 与早期肿瘤复发风险呈负相关 (P = 0.014),而 TLS 与总生存期之间未发现关联。Cox 回归分析确定 TLS 是早期 HCC 复发的独立预后因素 (P = 0.005)。此外,TLS 与瘤内 CD3 + 、 CD8 + 、 CD20 + 增加以及 Foxp3 + 和 CD68 + 细胞浸润减少有关。TLS + 病例中 PD1 + 、 TIM3 + 和 LAG3 + 密度较低。分分析揭示了 TLS 对早期 HCC (BCLC 0-A,TNM 分期 ⅰ-ⅱ) 和 HCC 伴孤立性结节的预后价值。验证队列验证了 TLS 在早期 HCC 患者中的预后价值。这些结果表明,TLS 靶向免疫调节疗法可能是有效免疫介导的肿瘤抑制的潜在策略。

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影响因子:2.46
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DOI:10.1097/COC.0000000000000609
作者列表:["Appelt AL","Andersen RF","Lindebjerg J","Jakobsen A"]

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