Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer




Punovuori, Karolina; Bertillot, Fabien; Miroshnikova, Yekaterina A.; Binner, Mirjam I.; Myllymäki, Satu-Marja; Follain, Gautier; Kruse, Kai; Routila, Johannes; Huusko, Teemu; Pellinen, Teijo; Hagström, Jaana; Kedei, Noemi; Ventelä, Sami; Mäkitie, Antti; Ivaska, Johanna; Wickström, Sara A.

PublisherElsevier BV

2024

Cell

Cell

187

25

7267

7284

0092-8674

1097-4172

DOIhttps://doi.org/10.1016/j.cell.2024.09.046

https://doi.org/10.1016/j.cell.2024.09.046

https://research.utu.fi/converis/portal/detail/Publication/459071031



Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution. By combining cell-state markers with morphological features, we identify phenotypic signatures that correlate with clinical features, including metastasis and recurrence. Integration of tumor and stromal signatures reveals that partial epithelial-mesenchymal transition (pEMT) renders disease outcome highly sensitive to stromal composition, generating a strong prognostic and predictive signature. Spatial transcriptomics and subsequent analyses of cancer spheroid dynamics identify the cancer-associated fibroblast-pEMT axis as a nexus for intercompartmental signaling that reprograms pEMT cells into an invasive phenotype. Taken together, we establish a paradigm to identify clinically relevant tumor phenotypes and discover a cell-state-dependent interplay between stromal and epithelial compartments that drives cancer aggression.


This work was supported by the Orion Foundation (to K.P. and Y.A.M.), Research Council of Finland (332402) and Turku Collegium for Science Medicine and Technologies postdoctoral grants (to G.F.), the Finnish Cancer Institute (to S.A.W. and K. Albin Johansson Professorship to J.I.), Academy of Finland Center of Excellence BarrierForce (#346131 to J.I. and S.A.W.), Academy of Finland Molecular Regulatory Networks of Life (#330033, NucleoMech; to A.M., J.I., and S.A.W.), and the Sigrid Juselius Foundation, Helsinki Institute of Life Science, Wihuri Research Institute, Business Finland R2B, and the Max Planck Society (all to S.A.W.).


Last updated on 2025-24-02 at 11:53