肝内胆管癌（ICC）是一种高度促纤维增生的肿瘤，即使在治愈性切除后预后也很差。我们研究了 ICC 基质组成与免疫细胞浸润之间的关联，旨在开发基质免疫特征来预测手术治疗 ICC 的预后。我们招募了 359 名 ICC 患者，并进行免疫组织化学检测 α-平滑肌肌动蛋白 (α- SMA)、CD3、CD4、CD8、Foxp3、CD68 和 CD66b。使用苯胺对胶原沉积进行染色。进行生存分析以检测这些标志物的预后值。应用离散时间生存树的递归分区来定义具有不同预后价值的基质免疫特征。我们根据免疫细胞亚群和基质组成描绘了一个综合的基质免疫特征，以区分具有不同无复发生存（RFS）和总生存（OS）时间的亚组。我们根据以下分布定义了 ICC 基质组成的四种主要模式： α-SMA 和胶原蛋白：休眠 (α-SMAlow/collagenhigh)、纤维化 (α-SMAhigh/collagenhigh)、惰性 (α-SMAlow/collagenlow) 和纤维溶解 (α-SMAhigh/collagenlow)。基质类型的特点是免疫细胞浸润的不同模式。我们将患者分为六类。 I 类以高 CD8 表达和休眠基质为特征，显示出最长的 RFS 和 OS，而 VI 类以低 CD8 表达和高 CD66b 表达为特征，显示出最短的 RFS 和 OS。整合的基质免疫特征在验证队列中得到巩固。我们开发并验证了基质免疫特征来预测手术治疗的 ICC 的预后。这些发现为 ICC 的基质免疫反应提供了新的见解。

Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC.We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time.We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort.We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.