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前哨淋巴结中 T 辅助细胞的激活预示着口腔鳞状细胞癌预后不良。

Activation of T helper cells in sentinel node predicts poor prognosis in oral squamous cell carcinoma.

机构信息

Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Sci Rep. 2020 Dec 18;10(1):22352. doi: 10.1038/s41598-020-79273-3.

Abstract

Recurrence in oral squamous cell carcinoma (OSCC) significantly reduces overall survival. Improved understanding of the host's immune status in head and neck cancer may facilitate identification of patients at higher risk of recurrence and improve patients' selection for ongoing clinical trials assessing the effectiveness of immune checkpoint inhibitors (CPI). We aimed to investigate Sentinel Node-derived T-cells and their impact on survival. We enrolled prospectively 28 OSCC patients treated at Karolinska University Hospital, Stockholm, Sweden with primary tumour excision and elective neck dissection. On top of the standard treatment, the enrolled patients underwent sentinel node procedure. T cells derived from Sentinel nodes, non-sentinel nodes, primary tumour and PBMC were analyzed in flow cytometry. Patients who developed recurrence proved to have significantly lower level of CD4+ CD69+ in their sentinel node (31.38 ± 6.019% vs. 43.44 ± 15.33%, p = 0.0103) and significantly higher level of CD8+ CD HLA-DR+ (38.95 ± 9.479% vs. 24.58 ± 11.36%, p = 0.0116) compared to disease-free individuals. Survival analysis of studied population revealed that patients with low proportion of CD4+ CD69+ had significantly decreased disease-free survival (DFS) of 19.7 months (95% CI 12.6-26.9) compared with 42.6 months (95% CI 40.1-45.1) in those with high CD4+ CD69+ proportion in their Sentinel Nodes (log-rank test, p = 0.033). Our findings demonstrate that characterization of T-cell activation in Sentinel Node serves as a complementary prognostic marker. Flow cytometry of Sentinel Node may be useful in both patients' surveillance and selection for ongoing CPI clinical trials in head and neck cancer.

摘要

口腔鳞状细胞癌 (OSCC) 的复发显著降低了总生存率。对头颈癌患者免疫状态的深入了解,可能有助于识别复发风险较高的患者,并改善患者选择参加正在评估免疫检查点抑制剂 (CPI) 有效性的临床试验。我们旨在研究前哨淋巴结衍生的 T 细胞及其对生存的影响。我们前瞻性地招募了 28 名在瑞典斯德哥尔摩卡罗林斯卡大学医院接受原发性肿瘤切除术和选择性颈部解剖的 OSCC 患者。除了标准治疗外,入组患者还接受了前哨淋巴结手术。通过流式细胞术分析前哨淋巴结、非前哨淋巴结、原发性肿瘤和 PBMC 中提取的 T 细胞。结果发现,发生复发的患者其前哨淋巴结中的 CD4+CD69+水平明显较低(31.38 ± 6.019%比 43.44 ± 15.33%,p = 0.0103),CD8+CD HLA-DR+水平明显较高(38.95 ± 9.479%比 24.58 ± 11.36%,p = 0.0116)。对研究人群的生存分析显示,前哨淋巴结中 CD4+CD69+比例低的患者无疾病生存率(DFS)明显降低(19.7 个月[95%CI 12.6-26.9]),而前哨淋巴结中 CD4+CD69+比例高的患者为 42.6 个月[95%CI 40.1-45.1](对数秩检验,p = 0.033)。我们的研究结果表明,前哨淋巴结中 T 细胞激活的特征可作为一种补充的预后标志物。前哨淋巴结的流式细胞术分析可能对患者监测和选择参加正在进行的头颈部癌症 CPI 临床试验都有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a60/7749121/4d9dd339b8df/41598_2020_79273_Fig1_HTML.jpg

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