Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.
Cancer Immunol Immunother. 2024 Jul 2;73(9):165. doi: 10.1007/s00262-024-03754-x.
Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers.
Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions.
Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8 T-cells and terminally exhausted PD-1TCF-1CD8 T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes.
We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1 T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.
口腔鳞状细胞癌(OSCC)在早期阶段较为常见且预后良好,但一旦转移至淋巴结,其生存率会显著下降。通过生物标志物早期检测淋巴结转移,可改善 OSCC 的治疗策略。在此,我们探讨了肿瘤引流淋巴结(TDLNs)中的树突状细胞(DC)和细胞毒性 T 细胞作为潜在的生物标志物。
采用多参数流式细胞术分析 12 例 OSCC 患者手术切除的 TDLNs、区域非 TDLNs 中的 DC 和细胞毒性 T 细胞,并与 9 例良性疾病患者的淋巴结进行比较。
我们的结果显示 TDLN 中具有免疫抑制特征的常规 cDC1 比例较高。此外,TDLN 中 cDC1 上的 PD-L1 高表达与转移和/或复发风险相关。与健康淋巴结相比,TDLN 和非 TDLN 中记忆性 CD8+T 细胞和终末耗竭 PD-1+TCF-1+CD8+T 细胞水平升高。
我们得出结论,TDLN 中存在可引发抗肿瘤适应性反应的细胞,这表现为活化的 cDC1 和祖细胞样 TCF-1+T 细胞。cDC1 上高 PD-L1 表达提示 TDLN 转移和不良预后,提示 TDLN 中 DC 上的 PD-L1 可作为预后较差的 OSCC 患者的预测生物标志物。