Zuyin Li, Zhao Li, Qian Cheng, Changkun Zhang, Delin Ma, Jialing Hao, Zhuomiaoyu Chen, Yuzi Li, Jiaxi Zheng, Jie Gao, Jiye Zhu
Department of Hepatobiliary Surgery, Peking University Organ Transplantation Institute, Peking University People's Hospital, Beijing, 100044, China.
Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China.
Adv Sci (Weinh). 2025 Feb;12(7):e2412740. doi: 10.1002/advs.202412740. Epub 2024 Dec 24.
Intrahepatic cholangiocarcinoma (ICC) tumor cells and their interactions with the immune microenvironment, particularly at the leading-edge area, have been underexplored. This study employs single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) analysis on samples from the tumor core, adjacent non-tumorous tissue, and the leading-edge area of nine ICC patients. These findings indicate that tumor cells at the leading-edge area demonstrate enhanced proliferation and are tightly associated with the stroma, including endothelial cells and POSTN+ FAP+ fibroblasts. Notably, CD8+ T cells in this region exhibit a naive phenotype with low cytotoxicity and signs of exhaustion, likely due to compromised antigen presentation by antigen-presenting cells (APCs). The predominant CD8+ T cell subset, mucosal-associated invariant T (MAIT) cells, recruits SPP1+ macrophages within the stroma. This interaction, along with the presence of POSTN+ cancer-associated fibroblasts (CAFs) and endothelial cells, forms a unique "triad structure" that fosters tumor growth and ICC progression. The research highlights the intricate characteristics and interactions of ICC tumor cells in the leading-edge area, offering insights into potential therapeutic targets for intervention.
肝内胆管癌（ICC）肿瘤细胞及其与免疫微环境的相互作用，尤其是在前沿区域，尚未得到充分研究。本研究对9例ICC患者的肿瘤核心、邻近非肿瘤组织和前沿区域的样本进行了单细胞RNA测序（scRNA-seq）和空间转录组（ST）分析。这些发现表明，前沿区域的肿瘤细胞增殖增强，并与包括内皮细胞和POSTN+FAP+成纤维细胞在内的基质紧密相关。值得注意的是，该区域的CD8+T细胞表现出幼稚表型，细胞毒性低且有耗竭迹象，这可能是由于抗原呈递细胞（APC）的抗原呈递受损所致。主要的CD8+T细胞亚群，即黏膜相关恒定T（MAIT）细胞，在基质内募集SPP1+巨噬细胞。这种相互作用，连同POSTN+癌相关成纤维细胞（CAF）和内皮细胞的存在，形成了一种独特的“三联体结构”，促进肿瘤生长和ICC进展。该研究突出了前沿区域ICC肿瘤细胞的复杂特征和相互作用，为潜在的干预治疗靶点提供了见解。
