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

A1 Refereed original research article in a scientific journal

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

Authors: 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.

Publisher: Elsevier BV

Publication year: 2024

Journal: Cell

Journal name in source: Cell

Volume: 187

Issue: 25

First page : 7267

Last page: 7284

ISSN: 0092-8674

eISSN: 1097-4172

DOI: https://doi.org/10.1016/j.cell.2024.09.046(external)

Web address : https://doi.org/10.1016/j.cell.2024.09.046(external)

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/459071031(external)

Abstract

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.

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Funding information in the publication:
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.).