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

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

doi:10.1016/j.cell.2024.09.046

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

Cell. 2024 Dec 12;187(25):7267-7284.e20. doi: 10.1016/j.cell.2024.09.046. Epub 2024 Oct 28.

Authors

Karolina Punovuori¹, Fabien Bertillot², Yekaterina A Miroshnikova³, Mirjam I Binner⁴, Satu-Marja Myllymäki¹, Gautier Follain⁵, Kai Kruse⁶, Johannes Routila⁷, Teemu Huusko⁷, Teijo Pellinen⁸, Jaana Hagström⁹, Noemi Kedei¹⁰, Sami Ventelä¹¹, Antti Mäkitie¹², Johanna Ivaska¹³, Sara A Wickström¹⁴

Affiliations

¹ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
² Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
³ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
⁵ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
⁶ Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
⁷ Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
⁸ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
⁹ Department of Oral Pathology and Radiology, University of Turku, Turku University Hospital, Turku, Finland; Research Programs Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki, 00014 Helsinki, Finland.
¹⁰ Collaborative Protein Technology Resource, Office of Science and Technology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹¹ Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
¹² Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, HUS, 00029 Helsinki, Finland; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute and Karolinska University Hospital, 17176 Stockholm, Sweden.
¹³ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Foundation for the Finnish Cancer Institute, Tukholmankatu 8, 00014 Helsinki, Finland.
¹⁴ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland; Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland. Electronic address: sara.wickstrom@mpi-muenster.mpg.de.

PMID: 39471809
DOI: 10.1016/j.cell.2024.09.046

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.

Keywords: cancer; cancer biomarker; cancer stem cell; epithelial-to-mesenchyme-transition.

MeSH terms

Animals
Cell Communication
Cell Line, Tumor
Epithelial-Mesenchymal Transition*
Female
Head and Neck Neoplasms* / metabolism
Head and Neck Neoplasms* / pathology
Humans
Male
Mice
Phenotype
Single-Cell Analysis
Squamous Cell Carcinoma of Head and Neck / metabolism
Squamous Cell Carcinoma of Head and Neck / pathology
Stromal Cells* / metabolism
Stromal Cells* / pathology
Tumor Microenvironment