Single-cell RNA sequencing analysis of intrahepatic cholangiocarcinoma reveals SPP1 facilitates disease progression via interaction with CD4(+) T cells.

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.