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肿瘤引流淋巴结中 T 调节细胞和免疫检查点表达对口腔鳞状细胞癌的预后价值

英文原题:Prognostic value of T regulatory cells and immune checkpoints expression in tumor-draining lymph nodes for oral squamous cell carcinoma.

查看英文原题

Prognostic value of T regulatory cells and immune checkpoints expression in tumor-draining lymph nodes for oral squamous cell carcinoma.

PubMed 2024/10/15(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

这些发现凸显了 TDLNs 在 OSCC 免疫微环境中的关键作用,并确立 T 细胞上免疫检查点表达作为有前景的预后生物标志物。这些见解提升了 OSCC 的预后框架,并为个体化治疗策略铺平了道路。TDLNs 的预后意义以及免疫检查点抑制剂的高表达,为采用新辅助免疫治疗提供了有力论据。

研究思路结论见上方概要

共纳入49例OSCC患者。每位患者分析一个TDLN,采用流式细胞术分析CD4+、CD8+和Tregs上的免疫检查点表达(PD-1、CTLA-4、TIGIT、TIM-3、LAG-3)及其他标志物如CD69、CXCR5。评估无病生存期(DFS)和总生存期(OS)。

根据多因素分析,TDLNs中FoxP3+CD4+和TIGIT+CD8+细胞水平升高与显著较差的DFS相关,而高CXCR5+CD4+水平与较好的DFS相关。值得注意的是,TDLNs内T细胞上免疫检查点的表达与复发状态显示出显著关联。经历复发的患者在TDLNs中表现出更高水平的T调节细胞、CD4+PD-1+和CD4+CTLA-4+细胞。生存多因素分析显示,T状态成为OS的独立预测因子。

展开英文摘要原文

Forty-nine OSCC patients were enrolled. One TDLN per patient was analysed using flow cytometry to profile immune-checkpoint expression (PD-1, CTLA-4, TIGIT, TIM-3, LAG-3) and other markers such as CD69, CXCR5 on CD4+, CD8+, and Tregs. Disease-free survival (DFS) and overall survival (OS) were assessed.

According to multivariate analysis, elevated levels of FoxP3+CD4+ and TIGIT+CD8+ cells in TDLNs correlated with significantly worse DFS, while high CXCR5+CD4+ levels were associated with better DFS. Notably, the expression of immune checkpoints on T cells within TDLNs showed significant associations with recurrence status. Patients experiencing recurrence exhibited heightened levels of T regulatory cells, CD4+PD-1+ and CD4+CTLA-4+, cells in TDLNs. Survival multivariate analyses revealed that T status emerged as an independent predictor of OS.

The findings highlight the critical role of TDLNs in the immune microenvironment of OSCC and establish immune checkpoint expression on T cells as promising prognostic biomarkers. These insights upgrade the prognostic framework for OSCC and pave the way for individualized therapeutic strategies. The prognostic significance of TDLNs and a high expression of immune checkpoint inhibitors is a compelling argument for the adoption of neoadjuvant immunotherapy.

论文信息

作者
Piersiala K、Hjalmarsson E、Lagebro V、Farrajota Neves da Silva P、Bark R、Elliot A、Marklund L、Margolin G
单位
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.Sweden
期刊
Frontiers in immunology2024
原文标识
PubMed 39474426 · DOI 10.3389/fimmu.2024.1455426