Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.
Front Immunol. 2024 Oct 15;15:1455426. doi: 10.3389/fimmu.2024.1455426. eCollection 2024.
Despite the employment of extensive therapeutic strategies, OSCC recurrence and mortality rates persist at high levels. This underscores the shortcomings of current prognostic models and the urgency for refined biomarkers. This study explores the prognostic significance of tumor-draining lymph nodes (TDLNs) in OSCC, with a special focus on the quantification of T regulatory cells (Tregs) and the expression of immune checkpoints on T cells.
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.
尽管采用了广泛的治疗策略，口腔鳞状细胞癌（OSCC）的复发率和死亡率仍居高不下。这突显了当前预后模型的不足和对精细化生物标志物的迫切需求。本研究探讨了肿瘤引流淋巴结（TDLNs）在 OSCC 中的预后意义，特别关注 T 调节细胞（Tregs）的量化和 T 细胞上免疫检查点的表达。
纳入 49 例 OSCC 患者。对每位患者的一个 TDLN 进行分析，采用流式细胞术对免疫检查点表达（PD-1、CTLA-4、TIGIT、TIM-3、LAG-3）和其他标志物（CD4+、CD8+上的 CD69、CXCR5）进行分析。评估无病生存率（DFS）和总生存率（OS）。
多变量分析显示，TDLNs 中 FoxP3+CD4+和 TIGIT+CD8+细胞水平升高与 DFS 显著相关，而 CXCR5+CD4+水平升高与 DFS 相关。值得注意的是，TDLNs 中 T 细胞上免疫检查点的表达与复发状态有显著关联。复发患者的 TDLNs 中 T 调节细胞、CD4+PD-1+和 CD4+CTLA-4+细胞水平升高。生存多变量分析显示 T 分期是 OS 的独立预测因子。
这些发现强调了 TDLNs 在 OSCC 免疫微环境中的关键作用，并确立了 T 细胞上免疫检查点的表达作为有前途的预后生物标志物。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 的预后意义和高表达免疫检查点抑制剂为采用新辅助免疫治疗提供了有力论据。
