Lin Xian, Peng Huanyan, Liu Ke, Chen Wenqi, Shao Ximing, Ning Chun, Li Hongchang, Yang Dongye
Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P.R. China.
Department of Pathology, Tianjin Medical University General Hospital, Tianjin 300050, P.R. China.
Oncol Lett. 2025 Jun 10;30(2):390. doi: 10.3892/ol.2025.15135. eCollection 2025 Aug.
Intrahepatic cholangiocarcinoma (ICC) is an aggressive form of cancer, characterized by limited treatment options and a poor prognosis. Immunological therapy is an emerging and promising strategy that has the potential to enhance treatment outcomes and extend the survival of patients with ICC. The role of CD4 T cells in the development of cancer has attracted attention in previous years. However, the complexities of the tumor microenvironment (TME) impede the full understanding of the roles of CD4 T cells in cancer. The present study used single-cell RNA sequencing to explore the heterogeneity of the TME during the development of ICC. The results demonstrated that CD4 T cells were enriched in the TME of ICC and the ratio of regulatory T cells (CD4-forkhead box P3) to central memory T cells (CD4-interleukin 7 receptor) was markedly increased. Secreted phosphoprotein 1 (SPP1) and CD44 showed increased expression levels in tumor cells and T cells from ICC tumor tissues, respectively. Additionally, SPP1 gene expression levels were higher and the ratio of regulatory T cells to central memory T cells was increased in the late stage of ICC compared with the early stage. Elevated levels of SPP1 were associated with a poor prognosis for patients with ICC. Finally, analysis of cell-cell interactions, utilizing established receptor-ligand pairs, demonstrated that ICC tumor cells may engage with immune cells through an SPP1-CD44 axis. Therefore, the results suggest that ICC tumor cells impact CD4 T-cell differentiation, which could alter the immune TME in ICC and potentially promote ICC tumor progression.
肝内胆管癌（ICC）是一种侵袭性癌症，其特点是治疗选择有限且预后较差。免疫疗法是一种新兴且有前景的策略，有可能改善ICC患者的治疗效果并延长其生存期。近年来，CD4 T细胞在癌症发展中的作用已引起关注。然而，肿瘤微环境（TME）的复杂性阻碍了对CD4 T细胞在癌症中作用的全面理解。本研究使用单细胞RNA测序来探索ICC发展过程中TME的异质性。结果表明，CD4 T细胞在ICC的TME中富集，调节性T细胞（CD4-叉头框P3）与中央记忆T细胞（CD4-白细胞介素7受体）的比例显著增加。分泌磷蛋白1（SPP1）和CD44分别在ICC肿瘤组织的肿瘤细胞和T细胞中表达水平升高。此外，与早期相比，ICC晚期的SPP1基因表达水平更高，调节性T细胞与中央记忆T细胞的比例增加。SPP1水平升高与ICC患者的不良预后相关。最后，利用已建立的受体-配体对进行细胞间相互作用分析表明，ICC肿瘤细胞可能通过SPP1-CD44轴与免疫细胞相互作用。因此，结果表明ICC肿瘤细胞影响CD4 T细胞分化，这可能改变ICC中的免疫TME并潜在促进ICC肿瘤进展。
