PO.CL01.23 · 临床研究
空间解析的谱系与微环境重塑定义口腔鳞状细胞癌的转移进展
Spatially resolved lineage and microenvironmental remodeling define metastatic progression in oral squamous cell carcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：淋巴结转移是口腔鳞状细胞癌（OSCC）最强的预后因素，然而驱动转移演化的空间协调性细胞程序仍未得到充分定义。传统的批量（bulk）和单细胞转录组学方法无法保留组织结构，也无法解析恶性、基质和免疫区室在原位如何相互作用。
方法：我们对20例OSCC组织标本进行了Visium空间转录组学分析，包括正常上皮、无淋巴结转移的原发肿瘤（N⁻）、有淋巴结转移的原发肿瘤（N⁺）以及转移性淋巴结。使用SpatialCpie估计斑点内（intra-spot）细胞组成，使用CellChat推断细胞间信号网络，使用Monocle3重建跨转移连续谱的上皮谱系轨迹。
结果：空间图谱显示，侵袭性肿瘤前沿包含混合的恶性上皮、成纤维细胞和免疫细胞群，将其与更为均质的肿瘤核心区分开来。拟时序（pseudotime）分析表明，存在从正常到转移状态的连续上皮谱系进展，并伴随上皮可塑性增加和分化相关标志物的下调。基质分析显示，位于侵袭性上皮区域邻近处的成纤维细胞表型向基质重塑方向转变。转移性淋巴结表现出细胞毒性T细胞特征减少和B系细胞群扩增，提示转移微环境内存在免疫抑制。整合信号分析揭示了一条协调的通讯轴，将转移进展过程中的上皮状态转变、基质激活和免疫重塑联系起来。
结论：这一空间解析框架将转移性OSCC鉴定为一个由上皮可塑性、基质重编程和免疫适应所塑造的动态演化的多细胞生态系统。这些发现为淋巴结转移的发生提供了机制性见解，并突出了具有潜在生物标志物和治疗意义的微环境特征。
查看英文原文 English abstract
Background: Lymph node metastasis is the strongest prognostic factor in oral squamous cell carcinoma (OSCC), yet the spatially coordinated cellular programs that drive metastatic evolution remain insufficiently defined. Conventional bulk and single-cell transcriptomic methods cannot preserve tissue architecture or resolve how malignant, stromal, and immune compartments interact in situ .
Methods: We performed Visium spatial transcriptomics on 20 OSCC tissue specimens, including normal epithelium, primary tumors without nodal metastasis (N⁻), primary tumors with nodal metastasis (N⁺), and metastatic lymph nodes. SpatialCpie was used to estimate intra-spot cellular composition, CellChat to infer intercellular signaling networks, and Monocle3 to reconstruct epithelial lineage trajectories across the metastatic continuum.
Results: Spatial mapping revealed that invasive tumor fronts contained mixed malignant epithelial, fibroblast, and immune populations, distinguishing them from more homogeneous tumor cores. Pseudotime analysis demonstrated a continuous epithelial lineage progression from normal to metastatic states, accompanied by increased epithelial plasticity and downregulation of differentiation-associated markers. Stromal profiling showed a shift toward matrix-remodeling fibroblast phenotypes positioned adjacent to invasive epithelial regions. Metastatic lymph nodes exhibited reduced cytotoxic T-cell signatures and expansion of B-lineage populations, indicating immune suppression within the metastatic niche. Integrated signaling analysis revealed a coordinated communication axis linking epithelial state transition, stromal activation, and immune remodeling during metastatic progression.
Conclusions: This spatially resolved framework identifies metastatic OSCC as a dynamically evolving multicellular ecosystem shaped by epithelial plasticity, stromal reprogramming, and immune adaptation. These findings provide mechanistic insight into the development of nodal metastasis and highlight microenvironmental features with potential biomarker and therapeutic relevance.
利益披露 Disclosure
C. LIu, None..
K. Chang, None.