本研究旨在探讨肿瘤微环境（TME）内肿瘤相关内皮细胞（TEC）和免疫细胞之间的相互作用及其对肿瘤预后的影响。我们对从肝内胆管癌 (ICC) 患者获得的肿瘤、正常组织和淋巴结组织进行了单细胞 RNA 测序 (scRNA-seq)，以揭示 TEC 在肿瘤血管生成中的作用及其显着的异质性。同时，我们鉴定了TEC中高表达的基因并构建了TEC签名（TEC.Sig）。接下来，我们根据 TEC.Sig 计算了样品的 TEC 分数。 TEC 评分较高的患者表现出较高的 KRAS 突变频率，这与中性粒细胞和未成熟树突状细胞 (iDC) 浸润增加以及自然杀伤 (NK)、CD4  T 和 CD8  T 效应记忆 (Tem) 数量减少相关细胞，表明炎症主导的免疫抑制表型。相反，BAP1突变和CXCL12过表达呈现出相反的趋势。空间转录组学分析和组织学实验进一步证实TECs通过CXCL12/CXCR4轴与多种肿瘤杀伤免疫细胞相互作用。多个肿瘤免疫治疗数据集证实 TEC.Sig 可以预测患者对免疫治疗的反应。 TEC 评分是预测 ICC 患者基因突变和预后的有前途且可靠的生物标志物。增强 CXCL12/CXCR4 信号通路的调节可能代表 ICC 治疗的潜在新治疗靶点。© 2024。作者。

This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune cells within the tumor microenvironment (TME) and its impact on tumor prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, and lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients to reveal the role of TECs in tumor angiogenesis and their significant heterogeneity. Meanwhile, we identified genes highly expressed in TECs and constructed TEC signatures (TEC.Sig). Next, we calculated TEC scores of samples based on TEC.Sig. Patients with higher TEC scores exhibited a higher frequency of KRAS mutations, which was associated with increased infiltration of neutrophils and immature dendritic cells (iDCs), and decreased numbers of natural killer (NK), CD4 + T, and CD8 + T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations and CXCL12 overexpression showed a contrasting trend. Spatial transcriptomics analysis and histological experiments further confirmed that TECs interacted with various tumor-killing immune cells through the CXCL12/CXCR4 axis. Multiple tumor immunotherapy datasets confirmed that the TEC.Sig could predict patient responses to immunotherapy. The TEC score is a promising and reliable biomarker for predicting genetic mutations and prognosis in ICC patients. Enhancing the regulation of the CXCL12/CXCR4 signaling pathway may represent a potential novel therapeutic target for ICC treatment.© 2024. The Author(s).