Multimodal single-cell profiling reveals crosstalk between macrophages and stromal cells in poor prognostic cholangiocarcinoma patients

Cholangiocarcinoma (CCA) is a deadly cancer, characterized by abundant stroma. The tumor microenvironment (TME) plays an important role in its aggressive behavior and poor response to therapeutics; however, the underlying pathways are unknown. To fill this gap, we used multiplexed immunohistochemistry, high-dimensional cytometry, and single cell transcriptomics. Our findings confirm an abundance of regulatory T cells (Tregs) and a lack of effector memory T cells within the tumor. Tumor-infiltrating T cells show signs of exhaustion. Using our transcriptomic data, we revealed cellular crosstalk in poor prognosis patients. This crosstalk is driven by stromal cells and macrophages. Among the responsible receptor-ligand pairs are GAS6-AXL, VCAN-TLR2, and EGFR-TGF-

• Heij, L.
• Hayat, S.
• Reichel, K.
• Maryam, S.
• O'Rourke, C. J.
• Tan, X.
• van den Braber, M.
• Verhoeff, J.
• Halder, M.
• Peisker, F.
• Wiltberger, G.
• Bednarsch, J.
• Heise, D.
• Deierl, J. C.
• Lang, S. A.
• Ulmer, F.
• Luedde, T.
• Dahl, E.
• Jonigk, D.
• Nolting, J.
• Sivakumar, S.
• Siveke, J.
• Vondran, F.
• Rocha, F. G.
• Baba, H. A.
• Hartmann, S.
• Andersen, J. B.
• Hobloss, Z.
• Ghallab, A.
• Hengstler, J. G.
• Vallejo, J. J. G.
• Kramann, R.
• Neumann, U.