PO.TB10.02 · 肿瘤生物学
空间解析的SEED（基质富集转移决定者）生态位整合肿瘤、基质和免疫生态系统以促成LUAD的淋巴结播散
Spatially resolved SEED (stromal-enriched metastatic decider) niches integrate tumor, stromal, and immune ecosystems to enable lymph node dissemination in LUAD
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的：肺腺癌（LUAD）表现出显著的瘤内异质性，但引发淋巴结转移的确切原发肿瘤亚区域仍不清楚。我们旨在利用配对的单细胞分辨率空间转录组学，鉴定具有转移能力的SEED区域并表征其微环境背景。
方法：使用10x Genomics Xenium 5K panel对17例LUAD患者的福尔马林固定组织进行分析，生成来自原发肿瘤和匹配淋巴结转移灶的配对数据集。使用Seurat和SpatialData进行空间和转录整合，并使用Scanpy计算元评分（metascore）和差异表达分析。
结果：原发-淋巴结整合分析揭示了一个反复出现的肿瘤细胞簇，其转录状态与淋巴结谱最为接近，代表了一个具有转移能力的SEED细胞群。SEED区域表现出升高的元评分以及侵袭和缺氧相关程序的富集，包括显著的HIF1A上调。周围微环境在空间上截然不同：紧邻seed簇的成纤维细胞表现出高POSTN表达，形成致密的基质外壳，而CXCR4高表达的B细胞聚集体则在瘤周积累。相比之下，T细胞分布在各区域之间保持相对均匀，表明SEED相关的重塑是由特定的基质和B细胞相互作用驱动的，而非普遍的免疫浸润。总的来说，这些空间协调的模式勾勒出一个生态位，其中HIF1A高表达的肿瘤细胞与富含POSTN的成纤维细胞以及表达CXCR4的B细胞相互作用，以支持转移能力。
结论：配对的单细胞空间图谱在LUAD原发肿瘤内鉴定出离散的、易于转移的SEED生态位。这些生态位由嵌入富含POSTN基质区室中的HIF1A高表达肿瘤细胞所定义，并被CXCR4高表达的B细胞聚集体所包围。这一空间生态系统为理解为何仅有特定的原发肿瘤区域获得淋巴结播散能力提供了机制框架，并提示了在生态位水平上进行转移拦截的靶点。
AI披露（AACR要求）：本摘要包含借助生成式AI修订的文本。
查看英文原文 English abstract
Purpose Lung adenocarcinoma (LUAD) displays substantial intratumoral heterogeneity, but the precise primary-tumor subregions that give rise to lymph-node metastasis remain unclear. We aimed to identify metastasis-competent SEED regions and characterize their microenvironmental context using paired single-cell-resolution spatial transcriptomics.
Methods Formalin-fixed tissues from 17 LUAD patients were profiled using the 10x Genomics Xenium 5K panel, generating paired datasets from primary tumors and matched lymph-node metastases. Spatial and transcriptional integration was performed using Seurat and SpatialData, and metascores and differential expression analyses were computed with Scanpy.
Results Integrated primary-lymph node analysis revealed a recurrent tumor-cell cluster whose transcriptional state aligned most closely with lymph-node profiles, representing a metastasis-competent SEED population. SEED regions showed elevated metascores and enrichment of invasion and hypoxia-associated programs, including robust HIF1A upregulation. The surrounding microenvironment was spatially distinct: fibroblasts immediately adjacent to seed clusters exhibited high POSTN expression, forming a dense stromal shell, while CXCR4-high B-cell aggregates accumulated peritumorally. In contrast, T-cell distribution remained relatively uniform across regions, indicating that SEED-associated remodeling was driven by specific stromal and B-cell interactions rather than general immune infiltration. Together, these spatially coordinated patterns delineate a niche in which HIF1A-high tumor cells interface with POSTN-rich fibroblasts and CXCR4-expressing B cells to support metastatic competence.
Conclusions Paired single-cell spatial mapping identifies discrete metastasis-prone SEED niches within LUAD primary tumors. These niches are defined by HIF1A-high tumor cells embedded in a POSTN-rich stromal compartment and surrounded by CXCR4-high B-cell aggregates. This spatial ecosystem provides a mechanistic framework for how only specific primary-tumor regions acquire the capacity for lymph-node dissemination and suggests niche-level targets for metastasis interception.
AI Disclosure (AACR-required) This abstract includes text revised with the assistance of generative AI.
利益披露 Disclosure
J. Oh, None..
H. Jeong, None..
Y. Choi, None..
D. Lee, None..
M. Lee, None.