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

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

2 Sitaatiot (Scopus)
4 Lataukset (Pure)

Abstrakti

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.

AlkuperäiskieliEnglanti
Sivut7267-7284.e20
JulkaisuCell
Vuosikerta187
Numero25
DOI - pysyväislinkit
TilaJulkaistu - 12 jouluk. 2024
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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