Several types of cancer spread through the lymphatic system via the sentinel lymph nodes (LNs). Such LN-draining primary tumors, modified by tumor factors, lead to the formation of a metastatic niche associated with an increased number of Foxp3+ regulatory T cells (Tregs). These cells are expected to contribute to the elaboration of an immune-suppressive environment. Activated Tregs express glycoprotein A repetitions predominant (GARP), which binds and presents latent transforming growth factor beta 1 (TGF-β1) at their surface. GARP is also expressed by other non-immune cell types poorly described in LNs. Here, we mapped GARP expression in non-immune cells in human and mouse metastatic LNs. The mining of available (human and murine) scRNA-Seq datasets revealed GARP expression by blood (BEC)/lymphatic (LEC) endothelial, fibroblastic, and perivascular cells. Consistently, through immunostaining and in situ RNA hybridization approaches, GARP was detected in and around blood and lymphatic vessels, in (αSMA+) fibroblasts, and in perivascular cells associated with an abundant matrix. Strikingly, GARP was detected in LECs forming the subcapsular sinus and high endothelial venules (HEVs), two vascular structures localized at the interface between LNs and the afferent lymphatic and blood vessels. Altogether, we here provide the first distribution maps for GARP in human and murine LNs.
多种类型的癌症通过前哨淋巴结（LNs）经淋巴系统扩散。受肿瘤因子影响的此类引流原发肿瘤的淋巴结，会形成与Foxp3+调节性T细胞（Tregs）数量增加相关的转移生态位。这些细胞被认为有助于形成免疫抑制环境。活化的Tregs表达富含甘氨酸-丙氨酸重复序列的蛋白（GARP），该蛋白在其表面结合并呈递潜伏转化生长因子β1（TGF-β1）。GARP也在淋巴结中其他尚未被充分描述的非免疫细胞类型中表达。本研究通过分析现有（人类和小鼠）单细胞RNA测序数据集，揭示了GARP在血液内皮细胞（BEC）/淋巴管内皮细胞（LEC）、成纤维细胞及血管周围细胞中的表达。通过免疫染色和原位RNA杂交技术，我们一致性地在血管和淋巴管内外、（αSMA+）成纤维细胞以及富含基质的血管周围细胞中检测到GARP表达。值得注意的是，在构成被膜下窦和高内皮微静脉（HEVs）的LECs中也检测到GARP表达，这两种血管结构位于淋巴结与输入淋巴管及血管的交界处。总之，本研究首次提供了GARP在人类和小鼠淋巴结中的分布图谱。
肿瘤(癌症)患者之家