Aoki Masaya, Kamimura Go, Harada-Takeda Aya, Nagata Toshiyuki, Murakami Gen, Ueda Kazuhiro
Department of General Thoracic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Anatomy, Tokyo Dental College, Tokyo, Japan.
J Anat. 2025 Mar 28. doi: 10.1111/joa.14251.
Nodal dendritic cells and CD169-positive macrophages cross-present cancer antigens earlier in the proximal nodes than in the distal nodes along the lymph flow from cancer. We examined topohistological differences between the proximal and distal nodes before the formation of metastasis. Immunohistochemical and morphometric analyses were performed to examine DC-SIGN-, CD68-, and CD169-positive cells in the subcarinal node (proximal) and paratracheal nodes (distal nodes) from 16 patients with lower-lobe lung cancer without metastasis (adenocarcinoma, 11; squamous, 5). Nodes at the same sites from 10 patients with upper-lobe cancer were used as controls. In all nodes, the medullary sinus was filled with CD68-positive and CD169-negative macrophages, most of which showed anthracosis. The proximal node carried a significantly smaller overlap between clusters of DC-SIGN-positive cells and CD169-positive cells relative to the distal node in lower-lobe cancer patients (p = 0.015). Irrespective of the cancer pathology, the tumor size was significantly correlated with the longer subcapsular clusters containing either DC-SIGN-positive cells or CD169-positive cells (p = 0.003, 0.043). A significantly small overlap between these clusters as well as the missing paracortical sinuses was evident in the negative control node outside the lymph flow (p = 0.006). Since DC-SIGN-positive cells and CD169-positive cells, especially composite cells in the overlapped cluster, are likely to be derived from monocytes, larger tumors appeared to accelerate the migration into the subcapsular sinus. In contrast to the suggested active status of the distal node, the proximal node appeared to have already been suppressed. This downregulation reached the level in the negative control node.
在沿癌症淋巴引流方向，结内树突状细胞和CD169阳性巨噬细胞在近端淋巴结比远端淋巴结更早地交叉呈递癌症抗原。我们在转移形成之前检查了近端和远端淋巴结之间的拓扑组织学差异。对16例无转移的下叶肺癌患者（腺癌11例；鳞癌5例）的隆突下淋巴结（近端）和气管旁淋巴结（远端淋巴结）进行免疫组织化学和形态计量分析，以检测DC-SIGN、CD68和CD169阳性细胞。将10例上叶癌患者相同部位的淋巴结用作对照。在所有淋巴结中，髓窦充满了CD68阳性和CD169阴性巨噬细胞，其中大多数显示有炭末沉着症。相对于下叶癌患者的远端淋巴结，近端淋巴结中DC-SIGN阳性细胞簇和CD169阳性细胞簇之间的重叠明显更小（p = 0.015）。无论癌症病理类型如何，肿瘤大小与包含DC-SIGN阳性细胞或CD169阳性细胞的较长被膜下簇显著相关（p = 0.003，0.043）。在淋巴引流外的阴性对照淋巴结中，这些簇之间的重叠明显较小以及副皮质窦缺失也很明显（p = 0.006）。由于DC-SIGN阳性细胞和CD169阳性细胞，特别是重叠簇中的复合细胞，可能来源于单核细胞，较大的肿瘤似乎加速了向被膜下窦的迁移。与远端淋巴结的活跃状态相反，近端淋巴结似乎已经受到抑制。这种下调达到了阴性对照淋巴结的水平。
