Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Cell Rep. 2022 Aug 16;40(7):111171. doi: 10.1016/j.celrep.2022.111171.
Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DRCD80CD86ICAM1PD-L1) and stimulate T cells (CD27Ki67PD-1). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1 immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.
肿瘤引流淋巴结 (LNs) 在癌症转移和启动抗肿瘤适应性免疫中起着至关重要的作用。中性粒细胞在 LNs 中形成了一个具有未知功能的大量细胞群体。在这里，我们证明在头颈部癌症 (HNC) 进展过程中，肿瘤相关中性粒细胞迁移到 LNs，并以阶段依赖的方式塑造抗肿瘤反应。在无转移阶段 (N0)，中性粒细胞表现出抗原呈递表型 (HLA-DR+CD80+CD86+ICAM1+PD-L1+)，并刺激 T 细胞 (CD27+Ki67+PD-1+)。LN 转移释放 GM-CSF，并通过 STAT3 触发 PD-L1 免疫抑制中性粒细胞的发展，抑制 T 细胞反应。在 N0 期的 LNs 中富含 T 细胞的区域中中性粒细胞的积累是 5 年生存率的一个积极预测指标，而在 N1-3 期的 LNs 中中性粒细胞数量的增加预示着 HNC 的预后不良。这些结果表明中性粒细胞在 LNs 中作为抗肿瘤免疫的重要调节剂具有双重作用，并为在癌症治疗期间促进这些细胞的免疫刺激活性的方法提供了依据。
